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NEURO (A) 2006 <681> Database EMBASE Accession Number 2006292404 Authors Ericson M. Molander A. Stomberg R. Soderpalm B. Institution (Ericson, Molander, Stomberg, Soderpalm) Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Goteborg University, Bla Straket 15, 413 45, Goteborg, Sweden. (Soderpalm) Beroendekliniken, Sahlgrenska University Hospital, Goteborg, Sweden. (Ericson) Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Bla Straket 15, 413 45 Goteborg, Sweden. Country of Publication United Kingdom Title Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Source European Journal of Neuroscience. 23(12)(pp 3225-3229), 2006. Date of Publication: Jun 2006. Abstract The mesolimbic dopamine (DA) system, projecting from the ventral tegmental area (VTA) to the nucleus accumbens (nAcc), is involved in reward-related behaviours and addictive processes, such as alcoholism and drug addiction. It was recently suggested that strychninesensitive glycine receptors (GlyR) in the nAcc regulate both basal and ethanol-induced mesolimbic DA activity via a neuronal loop involving endogenous activation of nicotinic acetylcholine receptors (nAChR) in the VTA. However, as the nAcc appears to contain few glycine-immunoreactive cell bodies or fibres, the question as to what may be the endogenous ligand for GlyRs in this brain region remains open. Here we have investigated whether the amino acid taurine could serve this purpose using in vivo microdialysis in awake, freely moving male Wistar rats. Local perfusion of taurine (1, 10 or 100 mm in the perfusate) increased DA levels in the nAcc. The taurine (10 mm)-induced DA increase was, similarly to that previously observed after ethanol, completely blocked by (i) perfusion of the competitive GlyR antagonist strychnine in the nAcc, (ii) perfusion of the nAChR antagonist mecamylamine (100 mum) in the VTA, and (iii) systemic administration of the acetylcholine-depleting drug vesamicol (0.4 mg/kg, i.p). The present results suggest that taurine may be an endogenous ligand for GlyRs in the nAcc and that the taurine-induced elevation of DA levels in this area, similarly to that observed after local ethanol, is mediated via a neuronal loop involving endogenous activation of nAChRs in the VTA. copyright The Authors (2006). ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 23 Issue Part 12 Page 3225-3229 Year of Publication 2006 Date of Publication Jun 2006 NEURO 2006 <693> Database EMBASE Accession Number 2006273145 Authors Raivich G. Behrens A. Institution (Raivich) Perinatal Brain Repair Group, Department of Obstetrics and Gynaecology, University College London, 8696 Chenies Mews, London, WC1E 6HX, United Kingdom. (Raivich) Department of Anatomy, University College London, 86-96 Chenies Mews, London, WC1E 6HX, United Kingdom. (Behrens) Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom. Country of Publication United Kingdom Title Role of the AP-1 transcription factor c-Jun in developing, adult and injured brain. Source Progress in Neurobiology. 78(6)(pp 347-363), 2006. Date of Publication: Apr 2006. Abstract The transcription factor activator protein-1 (AP-1) consists of a variety of dimers composed of members of the Jun and Fos families of proteins. However, it is the up-regulation of c-jun that is a particularly common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. In view of the long list of excellent in depth overviews on the different members of the Jun family and associated molecules, the primary focus of the current paper is to focus on c-Jun specifically and discuss the evidence on the involvement of this transcription factor in ischaemia and stroke, in seizures, during learning and memory, or following axonal injury and during successful regeneration. Functional studies employing in vivo strategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a bipotential role of c-Jun, in mediating neurodegeneration and cell death, as well as in plasticity and repair. Phosphorylation of c-Jun, and the activation of its upstream kinases (Jun N-terminal Kinase (JNK) 1-3, JNK kinases (JNKK)) is required in many but not in all forms of these events, with only a partial overlap of the Jun-, JNK- or JNKK(n)-dependent functions. Moreover, a better understanding of the non-overlapping roles could considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, or neurodegenerative disease. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0301-0082 Publication Type Journal: Review Journal Name Progress in Neurobiology Volume 78 Issue Part 6 Page 347-363 Year of Publication 2006 Date of Publication Apr 2006 NEURO 2006 <710> Database EMBASE Accession Number 2006263039 Authors McCarty M.F. Institution (McCarty) Natural Alternatives International, 1185 Linda Vista Dr, San Marcos, CA 92078, United States. Country of Publication United Kingdom Title Down-regulation of microglial activation may represent a practical strategy for combating neurodegenerative disorders. Source Medical Hypotheses. 67(2)(pp 251-269), 2006. Date of Publication: 2006. Abstract Chronic neurodegenerative disorders are characterized by activation of microglia in the affected neural pathways. Peroxynitrite, prostanoids, and cytokines generated by these microglia can potentiate the excitotoxicity that contributes to neuronal death and dysfunction in these disorders - both by direct effects on neurons, and by impairing the capacity of astrocytes to sequester and metabolize glutamate. This suggests a vicious cycle in which the death of neurons leads to microglial activation, which in turn potentiates neuronal damage. If this model is correct, measures which down-regulate microglial activation may have a favorable effect on the induction and progression of neurodegenerative disease, independent of the particular trigger or target involved in a given disorder. Consistent with this possibility, the antibiotic minocycline, which inhibits microglial activation, shows broad utility in rodent models of neurodegeneration. Other agents which may have potential in this regard include PPARgamma agonists, genistein, vitamin D, COX-2 inhibitors, statins (and possibly policosanol), caffeine, cannabinoids, and sesamin; some of these agents could also be expected to be directly protective to neurons threatened with excitotoxicity. To achieve optimal clinical outcomes, regimens which down-regulate microglial activation could be used in conjunction with complementary measures which address other aspects of excitotoxicity. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0306-9877 Publication Type Journal: Article Journal Name Medical Hypotheses Volume 67 Issue Part 2 Page 251-269 Year of Publication 2006 Date of Publication 2006 NEURO 2006 <740> Database EMBASE Accession Number 2006229085 Authors Pecina S. Schulkin J. Berridge K.C. Institution (Pecina, Berridge) Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States. (Schulkin) Department of Physiology and Biophysics, Georgetown University, CNE Branch, Washington, DC, United States. Country of Publication United Kingdom Title Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: Paradoxical positive incentive effects in stress? Source BMC Biology. 4, 2006. Article Number: 8. Date of Publication: 13 Apr 2006. Abstract Background: Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 mul) or amphetamine (20 mug/0.2 mul). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results: Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 mug) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. Conclusion: We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards. copyright 2006Pecina et al; licensee BioMed Central Ltd. ISSN 1741-7007 Publication Type Journal: Article Journal Name BMC Biology Volume 4 Year of Publication 2006 Date of Publication 13 Apr 2006 NEURO 2006 <751> Database EMBASE Accession Number 2006222678 Authors Boos T.L. Greiner E. Calhoun W.J. Prisinzano T.E. Nightingale B. Dersch C.M. Rothman R.B. Jacobson A.E. Rice K.C. Institution (Boos, Greiner, Calhoun, Prisinzano, Jacobson, Rice) Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8, Bethesda, MD 20892, United States. (Nightingale, Dersch, Rothman) Clinical Psychopharmacology Section, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224, United States. Country of Publication United Kingdom Title Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piper idine, an allosteric modulator of the serotonin transporter. Source Bioorganic and Medicinal Chemistry. 14(11)(pp 3967-3973), 2006. Date of Publication: 01 Jun 2006. Abstract A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl) piperidines with substituents at the ortho and meta positions in the aromatic ring of the N-benzyl side chain were synthesized and their affinities and selectivities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined. One analogue, 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piper idine (the C<sub>2</sub>-trifluoromethyl substituted compound), has been found to act as an allosteric modulator of hSERT binding and function. It had little affinity for any of the transporters. Several compounds showed affinity for the DAT in the low nanomolar range and displayed a broad range of SERT/DAT selectivity ratios and very little affinity for the NET. The pharmacological tools provided by the availability of compounds with varying transporter affinity and selectivity could be used to obtain additional information about the properties a compound should have to act as a useful pharmacotherapeutic agent for cocaine addiction and help unravel the pharmacological mechanisms relevant to stimulant abuse. ISSN 0968-0896 Publication Type Journal: Article Journal Name Bioorganic and Medicinal Chemistry Volume 14 Issue Part 11 Page 3967-3973 Year of Publication 2006 Date of Publication 01 Jun 2006 NEURO 2006 <762> Database EMBASE Accession Number 2006199552 Authors Ersche K.D. Clark L. London M. Robbins T.W. Sahakian B.J. Institution (Ersche, Sahakian) Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. (Ersche, Clark, Robbins, Sahakian) Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom. (Clark, Robbins) Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom. (London) Brookfields Hospital, Cambridge Drug and Alcohol Service, Cambridge, United Kingdom. (Sahakian) Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, Cambridgeshire CB2 2QQ, United Kingdom. Country of Publication United Kingdom Title Profile of executive and memory function associated with amphetamine and opiate dependence. Source Neuropsychopharmacology. 31(5)(pp 1036-1047), 2006. Date of Publication: May 2006. Abstract Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetaminedependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices. copyright 2006 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 31 Issue Part 5 Page 1036-1047 Year of Publication 2006 Date of Publication May 2006 NEURO 2006 <776> Database EMBASE Accession Number 2006185299 Authors Maldonado R. Valverde O. Berrendero F. Institution (Maldonado, Valverde, Berrendero) Laboratori de Neurofarmacologia, Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra, Carrer Dr. Aiguader 80, 08003 Barcelona, Spain. Country of Publication United Kingdom Title Involvement of the endocannabinoid system in drug addiction. Source Trends in Neurosciences. 29(4)(pp 225-232), 2006. Date of Publication: Apr 2006. Abstract Recent studies have shown that the endocannabinoid system is involved in the common neurobiological mechanism underlying drug addiction. This system participates in the primary rewarding effects of cannabinoids, nicotine, alcohol and opioids, through the release of endocannabinoids in the ventral tegmental area. Endocannabinoids are also involved in the motivation to seek drugs by a dopamine-independent mechanism, demonstrated for psychostimulants and opioids. The endocannabinoid system also participates in the common mechanisms underlying relapse to drug-seeking behaviour by mediating the motivational effects of drug-related environmental stimuli and drug re-exposure. In agreement, clinical trials have suggested that the CB<sub>1</sub> cannabinoid antagonist rimonabant can cause smoking cessation. Thus, CB<sub>1</sub> cannabinoid antagonists could represent a new generation of compounds to treat drug addiction. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0166-2236 Publication Type Journal: Review Journal Name Trends in Neurosciences Volume 29 Issue Part 4 Page 225-232 Year of Publication 2006 Date of Publication Apr 2006 NEURO (GENETICS) 2006 <805> Database EMBASE Accession Number 2006165643 Authors Lachman H.M. Institution (Lachman) Albert Einstein College of Medicine, Department of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, United States. Country of Publication United Kingdom Title An overview of the genetics of substance use disorders. Source Current Psychiatry Reports. 8(2)(pp 133-143), 2006. Date of Publication: Apr 2006. Abstract Twin, family, and adoption studies show that genetic factors play a significant role in vulnerability to becoming addicted to drugs. Through a combination of genetic approaches, the variant alleles responsible for interindividual differences in susceptibility to addiction are being uncovered. Copyright copyright 2006 by Current Science Inc. ISSN 1523-3812 Publication Type Journal: Review Journal Name Current Psychiatry Reports Volume 8 Issue Part 2 Page 133-143 Year of Publication 2006 Date of Publication Apr 2006 NEURO (A) 2006 <816> Database EMBASE Accession Number 2006152136 Authors Salinas A. Wilde J.D. Maldve R.E. Institution (Salinas, Wilde, Maldve) Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin, TX, United States. (Maldve) University of Texas at Austin, PHAR-Pharmacology, 1 University Station, Austin, TX 78712-0125, United States. Country of Publication United Kingdom Title Ethanol enhancement of cocaine- and amphetamine-regulated transcript mRNA and peptide expression in the nucleus accumbens. Source Journal of Neurochemistry. 97(2)(pp 408-415), 2006. Date of Publication: Apr 2006. Abstract Cocaine- and amphetamine-regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT-PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol-induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre-treatment significantly suppressed ethanol-enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol. copyright 2006 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 97 Issue Part 2 Page 408-415 Year of Publication 2006 Date of Publication Apr 2006 NEURO 2006 <826> Database EMBASE Accession Number 2006139224 Authors Hawes J.J. Narasimhaiah R. Picciotto M.R. Institution (Hawes, Narasimhaiah, Picciotto) Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States. (Picciotto) Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, United States. Country of Publication United Kingdom Title Galanin attenuates cyclic AMP regulatory element-binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures. Source Journal of Neurochemistry. 96(4)(pp 1160-1168), 2006. Date of Publication: Feb 2006. Abstract Repeated morphine administration leads to molecular alterations of the neural circuitry in the locus coeruleus and nucleus accumbens. These changes include increased activity of several components of the cAMP signaling pathway that are thought to be associated with psychological and somatic signs of opiate withdrawal. The neuropeptide galanin has been shown to attenuate cAMP signaling in multiple cell types. The current study demonstrates that acute galanin treatment blocks the consequences of increased cAMP signaling following chronic opiate administration and withdrawal in Cath.a cells and primary cultures of striatal neurons as measured by phosphorylation of the transcription factor cAMP regulatory elementbinding protein (CREB). In addition, galanin-mediated attenuation of CREB phosphorylation is independent of galanin-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in Cath.a cells. These data suggest that galanin receptors may serve as an additional potential therapeutic target for the treatment of opiate withdrawal. copyright 2006 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 96 Issue Part 4 Page 1160-1168 Year of Publication 2006 Date of Publication Feb 2006 NEURO 2006 <827> Database EMBASE Accession Number 2006137836 Authors Day J.J. Wheeler R.A. Roitman M.F. Carelli R.M. Institution (Day, Wheeler, Roitman, Carelli) Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, United States. Country of Publication United Kingdom Title Nucleus accumbens neurons encode Pavlovian approach behaviors: Evidence from an autoshaping paradigm. Source European Journal of Neuroscience. 23(5)(pp 1341-1351), 2006. Date of Publication: Mar 2006. Abstract Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS-, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS- were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed 'phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS- onset, while the inhibitory subpopulation showed no change in firing during the CS- period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans. copyright Federation of European Neuroscience Societies and Blackwell Publishing Ltd. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 23 Issue Part 5 Page 1341-1351 Year of Publication 2006 Date of Publication Mar 2006 OPIOIDS (A) 2006 <828> Database EMBASE Accession Number 2006137535 Authors Anton B. Leff P. Institution (Anton, Leff) Laboratory of Molecular Neurobiology and Addictive Neurochemistry, National Institute of Psychiatry, Ramon de la Fuente Muniz, Calz., Mexico D.F.C.P. 14370, Mexico. Country of Publication United Kingdom Title A novel bivalent morphine/heroin vaccine that prevents relapse to heroin addiction in rodents. Source Vaccine. 24(16)(pp 3232-3240), 2006. Date of Publication: 12 Apr 2006. Abstract Both pre-clinical and clinical studies make feasible the use of vaccines as novel therapeutic medications to treat drug addiction. No reports to date have shown the development of structural models of opiate candidate vaccines for treating human addiction to such compounds. Here we report on the initial development of a novel structural formulation of a bivalent vaccine against morphine/heroin. This vaccine was able to trigger and establish a high titer antibody response to haptenized drug with antibodies displaying equivalent specificities for both morphine and heroin. Such antibodies did not cross-recognize structurally dissimilar opiate medications. Furthermore, the evaluation of the potential therapeutic effectiveness of this vaccine was targeted to relapse prevention using a schedule of heroin delivery in the rat self-administration model. Antibodies against heroin blocked its reinforcing effects in rodents. The type of carrier protein used in this vaccine allows further evaluation of its potential therapeutic value for preventing relapse to heroin addiction in humans. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0264-410X Publication Type Journal: Article Journal Name Vaccine Volume 24 Issue Part 16 Page 3232-3240 Year of Publication 2006 Date of Publication 12 Apr 2006 NEURO 2006 <836> Database EMBASE Accession Number 2006130566 Authors Singh A. Das D.K. Kelley M.E. Institution (Singh) Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect Street, Burlington, VT 05401, United States. (Singh, Kelley) St. Mary's Regional Medical Center, Campus Avenue, Lewiston, ME 04243, United States. (Das) Androscoggin Valley Hospital, 59 Page Hill Road, Berlin, NH 03570, United States. Country of Publication United Kingdom Title Mecamylamine: Targacept. Source IDrugs. 9(3)(pp 205-217), 2006. Date of Publication: Mar 2006. Abstract Targacept Inc, under license from the University of South Florida, is developing a low-dose, liquid gel capsule formulation of the nicotinic acetylcholine antagonist mecamylamine, as a potential treatment for various neuropsychiatric disorders. copyright The Thomson Corporation. ISSN 1369-7056 Publication Type Journal: Article Journal Name IDrugs Volume 9 Issue Part 3 Page 205-217 Year of Publication 2006 Date of Publication Mar 2006 NEURO 2006 <857> Database EMBASE Accession Number 2006115334 Authors Ji S.-P. Zhang Y. Van Cleemput J. Jiang W. Liao M. Li L. Wan Q. Backstrom J.R. Zhang X. Institution (Ji, Zhang, Van Cleemput, Jiang, Zhang) Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Sask. S7N 5E4, Canada. (Liao, Li, Wan) Toronto Western Research Institute, University of Toronto, 399 Bathurst Street, Toronto, Ont. M5T 2S8, (Liao, Li, Wan) Department of Physiology, University of Toronto, 399 Bathurst Street, Toronto, Ont. M5T 2S8, Canada. (Backstrom) Department of Medicine, Vanderbilt University Medical Center, 21st Avenue South and Garland Avenue, Nashville, TN 37232, United States. Country of Publication United Kingdom Title Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse. Source Nature Medicine. 12(3)(pp 324-329), 2006. Date of Publication: Mar 2006. Abstract The widespread distribution of the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the adult brain<sup>1</sup> suggests its role in a broad range of brain functions. Here we show evidence supporting a physical interaction of PTEN with a region in the third intracellular loop (3L4F) of the serotonin 5-HT2C receptor (5HT2cR, formerly 5-HT1c receptor <sup>2</sup>) in cell cultures. PTEN limits agonist-induced phosphorylation of 5-HT2cR through its protein phosphatase activity. We showed the probable existence of PTEN:5-HT2cR complexes in putative dopaminergic neurons in the rat ventral tegmental area (VTA), a brain region in which virtually all abused drugs exert rewarding effects by activating its dopamine neurons<sup>3,4</sup>. We synthesized the interfering peptide Tat-3L4F, which is able to disrupt PTEN coupling with 5-HT2cR. Systemic application of Tat-3L4F or the 5-HT2cR agonist Ro600175 suppressed the increased firing rate of VTA dopaminergic neurons induced by Delta9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana. Using behavioral tests, we found that Tat-3L4F or Ro600175 blocks conditioned place preference of THC or nicotine, and that Ro600175, but not Tat-3L4F, produces anxiogenic effects, penile erection, hypophagia and motor functional suppression. These results suggest a potential strategy for treating drug addiction with the Tat-3L4F peptide. copyright 2006 Nature Publishing Group. ISSN 1078-8956 Publication Type Journal: Article Journal Name Nature Medicine Volume 12 Issue Part 3 Page 324-329 Year of Publication 2006 Date of Publication Mar 2006 NEURO (A) 2006 <858> Database EMBASE Accession Number 2006115321 Authors Carr D. Kalivas P.W. Institution (Carr, Kalivas) Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29645, United States. Country of Publication United Kingdom Title Orexin: A gatekeeper of addiction. Source Nature Medicine. 12(3)(pp 274-276), 2006. Date of Publication: Mar 2006. Abstract The neurotransmitter orexin regulates motivated behaviors such as arousal and feeding and is now implicated in behaviors associated with addiction in rats. The release of orexin onto dopamine cells enables cocaine to induce the neuronal changes that lead to addictionlike behavior. copyright 2006 Nature Publishing Group. ISSN 1078-8956 Publication Type Journal: Short Survey Journal Name Nature Medicine Volume 12 Issue Part 3 Page 274-276 Year of Publication 2006 Date of Publication Mar 2006 NEURO 2006 <910> Database EMBASE Accession Number 2006092239 Authors Ishiguro H. Liu Q.-R. Gong J.-P. Hall F.S. Ujike H. Morales M. Sakurai T. Grumet M. Uhl G.R. Institution (Ishiguro, Liu, Gong, Hall, Uhl) Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD, United States. (Ujike) Department of Neuropsychiatry, Okayama University Medical School, Okayama, Japan. (Morales, Uhl) Cellular Neuroscience Branch, NIDA-IRP, Baltimore, MD, United States. (Sakurai) Department of Neurobiology, Mt Sinai School of Medicine, New York, NY, United States. (Grumet) Keck Ctr. Collab. Neurosci., Rutgers University, Piscataway, NJ, United States. (Uhl) Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, United States. Country of Publication United Kingdom Title NrCAM in addiction vulnerability: Positional cloning, drug-regulation, haplotypespecific expression, and altered drug reward in knockout mice. Source Neuropsychopharmacology. 31(3)(pp 572-584), 2006. Date of Publication: Mar 2006. Abstract Several lines of evidence support roles for the cell adhesion molecule NrCAM in addictions. Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls. Differential display identifies NrCAM as a drug regulated gene. NrCAM is expressed in neurons linked to reward and memory. NrCAM displays haplotype-specific gene expression in human post-mortem brain samples. Knockout mice display reduced opiate- and stimulant-conditioned place preferences. These observations support NrCAM as a positionally cloned and drug-regulated gene whose variants are likely to change expression and alter substance abuse vulnerabilities in human addictions and animal models of drug reward. copyright 2006 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 31 Issue Part 3 Page 572-584 Year of Publication 2006 Date of Publication Mar 2006 NEURO 2006 <912> Database EMBASE Accession Number 2006086316 Authors Schlaepfer T.E. Lancaster E. Heidbreder R. Strain E.C. Kosel M. Fisch H.-U. Pearlson G.D. Institution (Schlaepfer, Kosel) Brain Stimulation Group, Department of Psychiatry, University Hospital, Bonn, Germany. (Schlaepfer, Lancaster, Strain, Pearlson) Division of Psychiatric Neuroimaging, Department of Psychiatry, Johns Hopkins Medical Institution, Baltimore, MD, United States. (Schlaepfer, Heidbreder, Kosel, Fisch) Psychiatric Neuroimaging Group, Department of Psychiatry, University Hospital, Bern, Switzerland. (Schlaepfer) Brain Stimulation Group, Department of Psychiatry, University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. Country of Publication United Kingdom Title Decreased frontal white-matter volume in chronic substance abuse. Source International Journal of Neuropsychopharmacology. 9(2)(pp 147-153), 2006. Date of Publication: Apr 2006. Abstract There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T<sub>2</sub> and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r = 0.65, p < 0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration. Copyright copyright 2005 CINP. ISSN 1461-1457 Publication Type Journal: Article Journal Name International Journal of Neuropsychopharmacology Volume 9 Issue Part 2 Page 147-153 Year of Publication 2006 Date of Publication Apr 2006 NEURO 2006 <934> Database EMBASE Accession Number 2006071032 Authors Schoenbaum G. Roesch M.R. Stalnaker T.A. Institution (Schoenbaum, Roesch, Stalnaker) Department of Anatomy and Neurobiology, University of Maryland School of Medicine, HSF-2 S251, 20 Penn Street, Baltimore, MD 21201, United States. (Schoenbaum) Department of Psychiatry, University of Maryland School of Medicine, HSF-2 S251, 20 Penn Street, Baltimore, MD 21201, United States. Country of Publication United Kingdom Title Orbitofrontal cortex, decision-making and drug addiction. Source Trends in Neurosciences. 29(2)(pp 116-124), 2006. Date of Publication: Feb 2006. Abstract The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in executive function. However, within this broad region, the orbitofrontal cortex is distinguished by its unique pattern of connections with crucial subcortical associative learning nodes, such as basolateral amygdala and nucleus accumbens. By virtue of these connections, the orbitofrontal cortex is uniquely positioned to use associative information to project into the future, and to use the value of perceived or expected outcomes to guide decisions. This review will discuss recent evidence that supports this proposal and will examine evidence that loss of this signal, as the result of drug-induced changes in these brain circuits, might account for the maladaptive decision-making that characterizes drug addiction. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0166-2236 Publication Type Journal: Review Journal Name Trends in Neurosciences Volume 29 Issue Part 2 Page 116-124 Year of Publication 2006 Date of Publication Feb 2006 NEURO 2006 <964> Database EMBASE Accession Number 2005581174 Authors Pierce R.C. Kumaresan V. Institution (Pierce, Kumaresan) Departments of Pharmacology and Psychiatry, Boston University School of Medicine, L603, 715 Albany Street, Boston, MA 02118, United States. (Kumaresan) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, 171 Meeting Street, Providence, RI 02912, United States. Country of Publication United Kingdom Title The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Source Neuroscience and Biobehavioral Reviews. 30(2)(pp 215-238), 2006. Date of Publication: 2006. Abstract In this review we will critically assess the hypothesis that the reinforcing effect of virtually all drugs of abuse is primarily dependent on activation of the mesolimbic dopamine system. The focus is on five classes of abused drugs: psychostimulants, opiates, ethanol, cannabinoids and nicotine. For each of these drug classes, the pharmacological and physiological mechanisms underlying the direct or indirect influence on mesolimbic dopamine transmission will be reviewed. Next, we evaluate behavioral pharmacological experiments that specifically assess the influence of activation of the mesolimbic dopamine system on drug reinforcement, with particular emphasis on animal experiments using drug self-administration paradigms. There is overwhelming evidence that all five classes of abused drugs increase dopamine transmission in limbic regions of the brain through interactions with a variety of transporters, ionotropic receptors and metabotropic receptors. Behavioral pharmacological experiments indicate that increased dopamine transmission is clearly both necessary and sufficient to promote psychostimulant reinforcement. For the other four classes of abused substances, self-administration experiments suggest that although increasing mesolimbic dopamine transmission plays an important role in the reinforcing effects of opiates, ethanol, cannabinoids and nicotine, there are also dopamine-independent processes that contribute significantly to the reinforcing effects of these compounds. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0149-7634 Publication Type Journal: Review Journal Name Neuroscience and Biobehavioral Reviews Volume 30 Issue Part 2 Page 215-238 Year of Publication 2006 Date of Publication 2006