SESSION 11: THE NEUROBIOLOGY OF ADDICTION – PAGE 1

The Neurobiology of AddictionJames D. Stoehr, Ph.D.

Professor, Midwestern University, Glendale, AZ623-572-3624 jstoehr@midwestern.edu

Signs and symptoms associated with substance abuse Loss of natural rewards, Escalation, Loss of control, Time devoted to drug

increases, Tolerance, Withdrawal, Continued harm

Addiction biomodels Abstinence, experimentation, social use, habituation, abuse, addiction

Nature Inherited genetic tendencies Neurochemical differences

Nurture Environment Stress

Progression from experimentation to addiction Due to genetics, environment and chemical makeup of drug

Overview of brain areas Brainstem Cerebellum Cerebral Cortical Areas

o Occipitalo Temporalo Parietalo Prefrontal cortex

Routes of administration Oral, venous,

respiratory... Can affect addictive

potential of drugs

Identification of brain pathways involved in addiction Self-injection in laboratory experiments

o Found various brain areas are sensitive to drugso Led to discovery of reward (pleasure) pathways

Ventral tegmental area (VTA) Targets throughout higher centers in brain

o Dopamine as neurotransmitter: released into synapses Projections into limbic system, prefrontal cortex and nucleus accumbens

o All shown to be sensitive to brain stimulation

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Nucleus accumbens (NAc) Small group of cells located

in the base of the forebrain Dopamine release

associated with subjective experience of pleasure

Involved with reward and reinforcement of ‘survival behaviors’

o Eating, drinking, reproduction, nurturing of offspring

Mechanisms of action of specific drugs of abuse

Nicotine, cocaine, amphetamines, etc.o Site of euphoric action

VTA, NAc dopamine transporter (DAT), etc.o Psychoactive drugs / other neurotransmitter interactions

Summary of regions involved in addiction: the vicious cycle Rate of progression from use to addiction

o Depends on genetics (DAT in NAc)o Depends on childhood abuse (corticosteroids?)o Depends on specific drug (rate of rise of DA)

All drugs push dopamine system o Reinforcement (euphoria)

Continued use impairs frontal cortexo Loss of behavioral controlo No regard for consequences of actions

Overview of frontal cortex involvement Prefrontal cortex system

o Lesions associated with irresponsible behavior, poor judgment Tracking, updating, modulating importance of reinforcer

o Controls and inhibits behavioral output Dysfunctional ventromedial orbitofrontal cortex:

o Overvaluing drug reinforcement / rewardo Undervaluing alternative reinforcement or consequences of actions / risk

Dysfunctional dorsolateral prefrontal cortex:o Sense of immediate gratification; Overactive in craving state

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Limbic structures implicated in addiction Amygdala

o Learns about social environment associated with drug use Hippocampus

o Memories associated with reinforcemento Euphoric recall

Insulao ‘what it feels like’ to crave

Disease vs. Accountability Introduction to ‘Neuro-ethics’ Is there a timepoint when accountability changes? see The American Journal of Bioethics,

January, 2007, 7(1) for review

Specific Cases as Examples Nicotine’s behavioral pharmacology Cocaine’s acute effects and clinical signs of abuse Methamphetamine’s chronic effects on the body and behavior Alcohol’s intoxication and different rates of tolerance PCP and ecstasy Opiates’ physiological effects Marijuana’s (THC’s) binding sites in the brain

Neurobiological Correlates of Steps Involved with Addiction and Recovery

Brain BehaviorGenetics, childhood, drug of choice May determine rate of progressionDopamine surge in NAc Extent of euphoria / drug seekingLimbic drives supersede cortical control Drug dependence and compulsivenessInternal or external signals cause change Sobriety soughtDrug free state (anti-craving medications) Drive cycles broken / recovery startsNatural rewards are reinforcing Interests in food, sleep, family returnHypothalamic balance Sleep cycles and appetite returnIncreased frontal cortex activity Emotional and impulse control returnsCognitive development Contentment in sobriety

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Current Biomodel of Relapse Stress activates NAc through PFC regions Context activates NAc through limbic areas (amygdale) NAc sensitive to drug reuse

Treatment Screening / Assessment

o Primary care physician or Crisis Center assessmento Specialists: Addictionist (ASAM certified), CSAC

Treatmento In-patiento Detox (hospital setting)o Rehab (14-28 days or more)o Out-patiento Rehab (Intensive Out-Patient)

Therapyo Individual counselingo Group

Support (family, friends, coworkers)

More information on substance abuse: National Institute on Alcohol Abuse and Alcoholism

o www.niaaa.nih.gov National Institute on Drug Abuse

o www.nida.nih.gov Substance Abuse and Mental Health Services Administration

o www.samhsa.org

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