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  • http://www.youtube.com/watch?v=oax3cUFsBSwALCOHOLCopyright Allyn & Bacon 2010*

  • Among Canadians 15 years and older, the prevalence of past-year cannabis use is 10.7% in 2010.Among Canadians 15 years and older, the prevalence of past-year cocaine or crack is 1.2% in 2010, past-year use of hallucinogens (0.9%), ecstasy (0.7%) and speed (0.5%)The rates of psychoactive pharmaceutical use and abuse: 26.0% of respondents aged 15 years and older indicated that they had used an opioid pain reliever, a stimulant, or a sedative or tranquilizer in the past year while 0.3% reported that they used any of these drugs to get high in the past year.Among Canadians 15 years and older, the prevalence of past-year alcohol use was 77.0%Cost over 40 billion dollars!DRUG STATS IN CANADACopyright Allyn & Bacon 2010*

  • 10% abstain from all alcohol use One of the highest rates of alcohol and drug addiction than anywhere else in Canada. More then 13% are struggling with drug addiction, alcoholism or both.These numbers work out to approximately two hundred thousand people at any one time are addicted to something. Police report that the number one cause of all domestic abuse cases in NL can be linked back to alcoholism and/or drug addiction.DRUG ABUSE IN NEWFOUNDLANDCopyright Allyn & Bacon 2010*

  • Common Features of AddictionCommonly Abused DrugsHeredity and Drug AbuseTherapy for Drug Abuse

    Lecture Preview

  • A Little BackgroundRecreational Drugs historically these are drugs discovered that produce pleasurable effects.One of the earliest recreational drugs was ethyl alcohol. Others include:OpiumCannabisCocaCoffeeTobaccoCOMMON FEATURES OF ADDICTION

  • Copyright Allyn & Bacon 2010*

    DrugSites of ActionEthyl alcoholNMDA receptor (indirect antagonist), GABAa receptor (indirect agonist)barbituratesGABAa receptor (indirect agonist)Benzodiazepines (tranquilizers)GABAa receptor (indirect agonist)Cannabis CB1 cannabinoid receptor (agonist)NicotineNicotinic ACh receptor (agonist)Opiates (heroin, morphine, etc) and Opiate receptor agonistPhencyclidine (PCP) and ketamineNMDA receptor (indirect antagonist)CocaineBlocks reuptake of dopamine (and 5-HT and NE)amphetamineCauses release of dopamine (running DA transporters in reverse)

  • Cocaine Blocks DA Re-Uptake in the Pre-Synaptic Cell: a DA Agonist

  • Positive ReinforcementAddictive drugs have reinforcing effectsEffectiveness of a reinforcing stimulus is greatest if it occurs immediately after a response occursMost addictive drugs are those that have immediate effectsDrug users prefer heroin to morphine not because effects are different, effects are fasterOnly a small percentage of people that try addictive drugs become dependentCocaine is one of the most addictive drugs currently available, ~ 15% of people who use it become addicted

    COMMON FEATURES OF ADDICTION

  • Neural MechanismsNatural reinforcers (food, water, sex) cause release of dopamine (DA) in the nucleus accumbens (NAC) mesolimbic pathwayAmphetamine, cocaine, opiates, alcohol, PCP, cannabis all trigger release of DA in NAC as measured by microdialysis

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural MechanismsDrugs hijack brain mechanisms that normally help us adapt to our environmentAddiction begins in mesolimbic DA system, produces long-term changes in brain regions that receive input from these neuronsCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • DA Pathway

  • Neural MechanismsVentral tegmental area (VTA)Single injection of addictive drug increased strength of excitatory synapses on DA neurons in VTA in mice Insertion of additional AMPA receptors into the postsynaptic membrane of DA neuronsSingle injection of drug produces synaptic strengthening in the VTA lasting 5 days, if drug given longer (2 weeks), changes in VTA persist

    COMMON MECHANISMS OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural MechanismsDue to changes in VTA, increased activation in regions that receive DA input from VTAVentral striatumNucleus accumbensDorsal striatum Caudate nucleus and putamen

    COMMON MECHANISMS OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural MechanismsAt 1st, addict experiences the pleasurable effects of drug, reinforcing behaviors (getting the drug, preparing it, swallowing, injecting, sniffing, smoking it, etc)

    Ventral striatum: nucleus accumbens Early reinforcing effects that take place in NAC encourage drug-taking behaviorCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural MechanismsSubsequent compulsive behaviors in addiction occur only after continued use of addictive drug

    Dorsal striatum: caudate nucleus and putamen

    Infusion of DA antagonist into dorsal striatum suppressed lever presses that had been reinforced by light that had been paired with cocaine

    Presence of a light that had previously been paired with IV cocaine increased DA release in the dorsal striatum, not ventral (NAC)

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural mechanismsIn humansWhen cocaine addicts are given an injection of methylphenidate, they show a much smaller release of DA in NAC or dorsal striatum than controls

    When people who were addicted to cocaine watched a video of people smoking cocaineIncreased release of DA was seen in dorsal striatum, not ventral striatumThe response to the drug itself is diminished in addicts, but the response to cues associated with the drug is augmented in the dorsal striatumCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural mechanismsOrexin and MCH play a critical role in the reinforcing effects of drugsOrexin (synthesized in LH) is released in VTA, NAC, dorsal striatumAdministration of addicted drugs or stimuli associated with them activate orexin neuronsInfusion of orexin into VTA causes relapseBlock of orexin in VTA blocks cocaine seeking elicited by drug-related cues and prevents CPP (place where morphine was previously administered) COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Neural mechanismsOrexin and MCH play a critical role in the reinforcing effects of drugsMCH (synthesized in LH) receptors in NAC MCH neurons also contain DA receptors in NACStimulating both DA receptors and MCH receptors increased firing of NAC neuronsBlock of MCH receptors decreased the effectiveness of cocaine or cocaine-related cues of the animals behaviorMutant MCH receptor had same effectCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Negative reinforcementA behavior that turns off (or reduces) an aversive stimulus will be reinforcedNot punishment makes behavior less likelyTolerance decrease in sensitivity to a drug that comes from repeated useWithdrawal symptoms primarily the opposite of the effects of the drugEffects of heroin euphoria, constipation, relaxationWithdrawal effects of heroin dysphoria, cramping and diarrhea, and agitation

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Negative ReinforcementTolerance bodys attempt to compensate for unusual conditionDrug disturbs normal homeostatic mechanisms in the brain compensatory responsesBecause of this compensation, user must take increasing amounts to achieve the original effects of the drugMechanisms also cause withdrawalWhen the person stops taking the drug, compensatory mechanisms make themselves felt unopposed by drugCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Positive reinforcement seems to be what provokes drug taking in the first placeReduction in withdrawal symptoms may play a role in maintaining drug addictionNegative reinforcement may also explain acquisition of drug addictions under some conditionsAlcohol to relieve feelings of anxiety

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Cravings and RelapseWhen an addictive drug activates the mesolimbic DA system, it gives incentive salience to stimuli present at that timeStimuli associated with drug become exciting and motivatingIncreases cravingsAnimal model of cravingsReinstatementAnimals are first trained to make a response (press a lever), that is reinforced by iv injections of drug (cocaine)Response is extinguished injections of saline instead of cocaineOnce the animal stops responding (pressing the lever), experimenter administers a free injection of drugIn response, animals begin pressing lever againCOMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Cravings and RelapseAnimal model reinstatementRelapses produced by unexpected dose of drug activate mesolimbic DA systemIf the NAC or VTA of rats is temporarily inactivated, free shot of cocaine fails to reinstate responding

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Cravings and RelapseExtinction new form of learning, animal does not forget to make a particular response, it learns not toVentromedial prefrontal cortex (vmPFC)Stimulation of vmPFC with infusion of AMPA blocked reinstatement produced by free shot of cocaineDorsal anterior cingulate cortex (dACC)Reinstatement of lever pressing for infusions of cocaine was abolished by injecting a GABA agonist into dACC region of dorsal PFC that has excitatory connections with NAC

    dACC plays a role in craving, vmPFC plays a role in suppression

    COMMON FEATURES OF ADDICTIONCopyright Allyn & Bacon 2010*

  • Craving and RelapseIn humansDrugs of abuse or cues associated with them activate several brain regionsAnterior cingulate cortex (ACC), orbitofrontal cortex (OFC), insula, dorsolateral PFC (dlPFC)

    COMMON FEATURES OF ADDICTIONCopyright Ally

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