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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