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CHAPTER 16 Drug Abuse and Autism Basic Lecture Outline with notes Substance Abuse Disorders Addiction Latin roots from addicere “to sentence” Physical vs. Psychological addiction Physical dependence – “an adaptive state that manifests itself by intense physical disturbances when the administration of the drug is suspended” Tolerance – decreased sensitivity to a drug from continued use. Withdrawal – opposite symptoms of the effects of the drug itself Psychic dependence – “a condition in which a drug produces a feeling of satisfaction and psychic drive that requires periodic or continuous administration of the drug to produce pleasure or to avoid discomfort“. Psychic dependence which is produced by stimulation of the nucleus accumbens is far more powerfully “addictive” than some drugs that produce physical dependence (Example: methamphetamine and cocaine produce psychic dependence that is more “addictive” than heroin.) Common Features of Drug Addiction Positive Reinforcement – The faster the reinforcement after the drug is used the more potent the reinforcement. Probably most significant reinforcer is the release of dopamine in the nucleus accumbens. (Heroin is more “addictive” or reinforcing than Morphine because it has a more rapid effect.) Negative Reinforcement – Drug turns off or reduces an aversive stimulus. (Alcohol reduces anxiety.) Craving – Stimuli around the use of the drug create an excitement of the brain and increase desire to use the drug, (example: the smell of the drug or the place where drug is acquired or people one uses the drug with become associated in the brain with drug use and create “craving” for the drug.) Relapse – Use of the drug produces permanent changes in structure of the brain, increased density of D3 receptors in nucleus accumbens, making more likely that a person will reinstate drug use behaviors. Stress can also make a person more vulnerable to drug use and reuse. Commonly Abused Drugs CNS Stimulants – elevate activity and alertness. They have an effect similar to the body’s own adrenaline or epinephrine. Depending on the dosage and type of CNS stimulant the effect range from increased alertness, felling of well-being, euphoria, anxiety, palpitations, tremors, convulsions and ultimately death. Amphetamine and Cocaine – Newsweek August 8, 2005 – “Cops nationwide rank methamphetamine the No. 1 drug they battle today: in a survey of 500 law-enforcement agencies in 45 states released in July by the National Association of Counties, 58 percent said meth is their biggest drug problem, compared with only 19 percent for cocaine, 17 percent for pot and 3 percent for heroin.” binds with and deactivates the dopamine reuptake transporter proteins – thus blocking the reuptake of dopamine after it is released by terminal buttons. Amphetamine not only inhibit reuptake of Dopamine, but also stimulates the release of Dopamine from the terminal buttons by causing the uptake pumps to run in reverse. Both drugs also have reinforcing effects on Dopamine receptors in the nucleus accumbens. These drugs produce long term structural changes in brain. Ritalin, Cylert –Used to treat ADHD or ADD. Although they are chemically not amphetamine, pharmacologically their effect is virtually identical. Preludin – Prescribed as an appetite-suppressant. Tolerance to the appetite-suppressant action appears with about two weeks. Then the dose is increased. Nicotine – Most commonly abused drug. Causes stimulation of acetylcholine synapses. Because it stimulated the CNS at all levels, including the cerebral cortex in produces increased levels of behavioral activity. Increases the activity of dopaminergic neurons on the mesolimbic system and causes dopamine to be released in the nucleus accumbens and the ventral tegmental area. CNS Depressants – Used as painkillers. Can also produce a feeling of relaxation, loss of inhibition or euphoria in smaller doses. Act on the brain like an anesthetic inducing drowsiness, sleep, loss of consciousness, convulsions and ultimately death depending on the dosage. Use of CNS depressants is ADDITIVE, can produce CROSS-TOLERANCE and CROSSDEPENDENCE Alcohol – most heavily abused drug. Has effect on GABAa receptors. Produces IPSPs, opening chloride channels, functioning as indirect agonist. It also acts as an indirect antagonist on NMDA receptors interfering with the effect of glutamate interfering with spatial receptive fields within the hippocampus, thus affecting memory and other cognitive functions. As with other addictive drugs, alcohol stimulates an increased the activity of the dopaminergic neurons of the mesolimic system and increases the release of dopamine in the nucleus accumbens. Opiates –Acts on GABAa and GABA b receptors. Natural or synthetic morphine – major pain relieving agent obtained from opium poppy. (Opiates – reduces pain and creates sense of euphoria. Barbiturates – induce sleep but don’t reduce pain) Cross – tolerance – tolerance to one opiate will also exhibit a tolerance to all natural or synthetic opiates, even if they are chemically dissimilar (example: Morphine/Heroin/Demerol/Percodan ) Barbiturates – Acts on GABAa receptors as indirect agonist similar to alcohol. Is not an analgesic. They are typically prescribed as sedatives. If pain is present, however, they may have little sedative or hypnotic effect. General Anesthetics – Volatile hydrocarbons, capable of inducing general anesthesia. Easily accessible(airplane glue, nail polish remover, lighter fluid, hairsprays, paint thinner, room deodorizer, laughing gas, and capable of inducing liver failure, nerve damage, heart failure, respiratory arrest, coma and ultimately death. Entactogens- “touching within” MDMA (Ecstasy). Produces a relaxed, euphoric state. Sensations are enhanced and the user experiences heightened feelings of empathy, emotional warmth, and self-acceptance. Does not produce hallucinations. Releases serotonin into synapse by causing reuptake pumps to work backwards, similar to the way cocaine and amphetamine cause dopamine reuptake pumps to reverse. Prolonged use has causes permanent neurotoxic damage in laboratory animals. There is speculation this action is similar in humans, the result would be felt as depression with the depletion of serotinergic neurons. Heredity and Drug Abuse “Most people who are exposed to addictive drugs – even drugs with high abuse potential- do not become addicted.. The likelihood of addiction, especially to alcohol and nicotine is strongly affected by heredity.’ Twp types of alcoholics appear to exist: Steady drinkers and binge drinkers. Steady drinkers usually begin drinking before age 25, are frequently unable to abstain once they begin drinking, tend to be antisocial and novelty seeking in their behavior. Binge drinkers on the hand, usually begin after age 25 and tend to be psychologically dependent, repressed and guilt-ridden about becoming alcohol dependant. Because of the cross-tolerant dependence many addicts have, alcoholic who stop drinking tend to “abuse” caffeine and nicotine excessively. Therapy for Drug Abuse Dsiulfiram (Antibuse) – Used to treat chronic alcoholism because it inhibits aldehyde dehydrogenase, an enzyme that carries out a specific stem in alcohol metabolism. Methadone is used for heroin and morphine addiction. It has approximately the same analgesic potency as morphine but induces less euphoria Naloxone– narcotic antagonists prevents euphoric effects of heroin or morphine–used to treat narcotic dependence. Autistic Disorder Description A chronic disorder first described in 1943 by Johns Hopkins psychiatrist Leo Kanner, and again in 1944 by Austrian pediatrician Hans Asperger. Symptoms include failure to develop normal social relations with other people, impaired development of communicative ability, lack of imaginative ability and repetitive, stereotyped movements. *Signs of Autism no pointing by 1 year no babbling by 1 year; no single words by 16 months; no two-word phrases by 24 months. Any loss of language skills at any time No pretend play Little interest in making friends Extremely short attention span No response when called by name; indifference to others Little or no eye contact Repetitive body movements, such as hand flapping rocking Intense tantrums Fixations on a single object, such as a spinning fan Unusually strong resistance to changes in routines Oversensitivity to certain sounds, textures or smells. *Signs of Asperger’s Difficulty making friends Difficulty reading or communicating through nonverbal social cues, such as facial expressions. No understanding that others may have thought or feelings different from his or her own Obsessive focus on a narrow interest, such as reciting train schedules Awkward motor skills Inflexibility about routines, especially when changes occur spontaneously Mechanical, almost robotic patterns of speech *(Even “normal” children exhibit some of theses behavior from time to time. The symptoms of autism and Asperger’s, by contrast, are persistent and debilitating.) Prevalence Until recently, autism was assumed to be rather rare. When Kanner first described it the incidence was thought to be 1:10,000. When your book was written the incidence was 1:2,500. The latest studies suggest as many as 1:150 children may be affected by autism or a related disorder, i.e. Asperger’s , Rett’s syndrome, Fragile X Syndrome Heritability Greater likelihood that two monozygotic twins (i.e. identical twins) will have autism is 70%.. The likelihood that two dizygotic twins (i.e. fraternal twins) is currently 0%. Genetic investigations have suggest that genes involved in autistic disorder may be located on chromosomes 2,7,15 and X.( Folstein and Rosen-Sheidley, 2001) Papers published in “Molecular Psychiatry” indicate intense scrutiny is being given genes that regulate the action of three powerful neurotransmitters: glutamate, serotonin, and GABA. But those aren’t the only ones. Your book also sites 20% of cases of autism have definable biological causes such as rubella (German measles) during pregnancy, ;prenatal thalidomide; encephalitis caused by the herpes virus, as well as autoimmune reaction provoked by streptococcal infection. There is growing concern that toxins, such as mercury, and pollution in the environment cal also lead to autism. (LA Times, Thursday, March 17, 2005, Section A10 “Possible Mercury, Autism connection Found in Study” by, Maugh, Thomas H. II. For several years there has been a controversy raging related to childhood vaccines and mercury in the preservative, thimerosal that was used in the vaccines. There is also a theory that autism stems from a severe immune reaction to something in the vaccine. So far, there is no absolute proof, Some speculate the symptoms appearance shortly after the MMR vaccine is coincidental. (Fifteen months is usually when the shots are given and is also the time when maladaptive behaviors and dysfunctional speech patterns in babies are more pronounced and thus, observed by parents. Additional sources: www.time.com Time Magazine, May 6, 2002,”The Secrets of Autism” Nash, J. Madeline, Pp. 45-56. http://www.nimh.nih.gov/publicat/autism.cfm http://www.autism.org/overview.html www.latimes.com