Neurobiology of Addiction



The Neurobiology of AddictionJames D. Stoehr, Ph.D.Professor, Midwestern University, Glendale, AZ623-572-3624 jstoehr@midwestern.edu Signs and symptoms associated with substance abuseLoss of natural rewards, Escalation, Loss of control, Time devoted to drug increases, Tolerance, Withdrawal, Continued harmAddiction biomodelsAbstinence, experimentation, social use, habituation, abuse, addictionNature Inherited genetic tendenciesNeurochemical differences NurtureEnvironmentStressProgression from experimentation to addictionDue to genetics, environment and chemical makeup of drug217170076200Overview of brain areasBrainstemCerebellumCerebral Cortical AreasOccipitalTemporalParietalPrefrontal cortexRoutes of administrationOral, venous, respiratory...Can affect addictive potential of drugsIdentification of brain pathways involved in addictionSelf-injection in laboratory experimentsFound various brain areas are sensitive to drugsLed to discovery of reward (pleasure) pathwaysVentral tegmental area (VTA)Targets throughout higher centers in brainDopamine as neurotransmitter: released into synapsesProjections into limbic system, prefrontal cortex and nucleus accumbensAll shown to be sensitive to brain stimulationNucleus accumbens (NAc)Small group of cells located in the base of the forebrainDopamine release associated with subjective experience of pleasureInvolved with reward and reinforcement of ‘survival behaviors’Eating, drinking, reproduction, nurturing of offspringMechanisms of action of specific drugs of abuseNicotine, cocaine, amphetamines, etc.Site of euphoric actionVTA, NAc dopamine transporter (DAT), etc.Psychoactive drugs / other neurotransmitter interactionsSummary of regions involved in addiction: the vicious cycle457200086360Rate of progression from use to addictionDepends on genetics (DAT in NAc)Depends on childhood abuse (corticosteroids?)Depends on specific drug (rate of rise of DA)All drugs push dopamine system Reinforcement (euphoria)Continued use impairs frontal cortexLoss of behavioral controlNo regard for consequences of actionsOverview of frontal cortex involvementPrefrontal cortex system Lesions associated with irresponsible behavior, poor judgmentTracking, updating, modulating importance of reinforcerControls and inhibits behavioral outputDysfunctional ventromedial orbitofrontal cortex:Overvaluing drug reinforcement / rewardUndervaluing alternative reinforcement or consequences of actions / risk Dysfunctional dorsolateral prefrontal cortex:Sense of immediate gratification; Overactive in craving stateLimbic structures implicated in addictionAmygdalaLearns about social environment associated with drug use365760088265HippocampusMemories associated with reinforcementEuphoric recall Insula‘what it feels like’ to craveDisease vs. AccountabilityIntroduction to ‘Neuro-ethics’Is there a timepoint when accountability changes?see The American Journal of Bioethics, January, 2007, 7(1) for reviewSpecific Cases as ExamplesNicotine’s behavioral pharmacologyCocaine’s acute effects and clinical signs of abuseMethamphetamine’s chronic effects on the body and behaviorAlcohol’s intoxication and different rates of tolerancePCP and ecstasyOpiates’ physiological effectsMarijuana’s (THC’s) binding sites in the brainNeurobiological Correlates of Steps Involved with Addiction and RecoveryBrainBehaviorGenetics, childhood, drug of choiceMay determine rate of progressionDopamine surge in NAcExtent of euphoria / drug seekingLimbic drives supersede cortical controlDrug dependence and compulsivenessInternal or external signals cause changeSobriety soughtDrug free state (anti-craving medications)Drive cycles broken / recovery startsNatural rewards are reinforcingInterests in food, sleep, family returnHypothalamic balanceSleep cycles and appetite returnIncreased frontal cortex activityEmotional and impulse control returnsCognitive developmentContentment in sobrietyCurrent Biomodel of RelapseStress activates NAc through PFC regionsContext activates NAc through limbic areas (amygdale)NAc sensitive to drug reuseTreatmentScreening / AssessmentPrimary care physician or Crisis Center assessmentSpecialists: Addictionist (ASAM certified), CSACTreatmentIn-patientDetox (hospital setting)Rehab (14-28 days or more)Out-patientRehab (Intensive Out-Patient)TherapyIndividual counselingGroupSupport (family, friends, coworkers)More information on substance abuse:National Institute on Alcohol Abuse and Alcoholismniaaa.National Institute on Drug Abusenida. Substance Abuse and Mental Health Services Administration ................
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