The Biology of Addiction

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1 The Biology of Addiction

2 Risk factors for addiction: Biological/Genetic Family history of addiction Being male Having mental illness Exposure to substances in utero * The genes that people are born with account for about half of a person's risk for addiction.

3 Risk factors for addiction: Environmental Lack of family involvement/abuse/chaotic household Peer pressure Poor social skills Parents' use and attitudes Poor school performance Taking highly addictive drug (route of administration) Availability of drugs, early use Trauma Community poverty

4

5 The Neurobiology of Substance Use Disorders is Complex There are significant differences between: What gets us to use What keeps us using What keeps us from stopping What gets us using again AND each of these processes has multiple interactions with different brain circuits

6 Hijacking the Dopamine-Fueled Reward System

7 Reward Pathway Specialized brain areas for producing and regulating DRIVES Ventral Tegmental Area Nucleus Accumbens Prefrontal Cortex Areas of Limbic system amygdala, hippocampus, hypothalamus

8 Functional Divisions: Cut Brain View Neuroscience of Addiction Day 2 8

9 Dopamine Key role in animal attraction Allows for the intense focus for drives Food, water Elevated brain levels associated with passionate love Neurotransmitter of addiction Many other functions in human brain

10 Dopamine receptors: Distribution

11 Reward Circuit Currency of reward circuit is dopamine All abused drugs have a common end point: Increased dopamine levels in the shell of the nucleus accumbens Drugs activate the pathway with force and persistence not seen with natural rewards

12 Drug effects on neurotransmission Alcohol, heroin, nicotine excite the dopamine neurons in the VTA to increase dopamine release

13 Dopamine Levels around Nucleus Accumbens and Reported High

14 Natural Rewards Elevate Dopamine 200 FOOD NAc shell % of Basal DA Output Empty Box Feeding Time (min) Source: Di Chiara et al.

15 Natural Rewards Elevate Dopamine DA Concentration (% Baseline) Sample Number Scr Scr Bas Female 1 Present SEX Mounts Intromissions Ejaculations Scr Source: Fiorino and Phillips Scr Female 2 Present Copulation Frequency

16 Effects of Drugs on Dopamine Release % of Basal Release Accumbens AMPHETAMINE hr Time After Amphetamine DA DOPAC HVA % of Basal Release Accumbens COCAINE DA DOPAC HVA hr Time After Cocaine 250 NICOTINE 250 Accumbens ETHANOL % of Basal Release hr Time After Nicotine Accumbens Caudate % of Basal Release Dose (g/kg ip) hr Time After Ethanol Source: Di Chiara and Imperato

17 Natural Rewards Elevate Dopamine % of Basal DA Output Empty Box FOOD Feeding NAc shell Time (min) DA Concentration (% Baseline) Sample Number Scr Scr Bas Female 1 Present SEX Scr Mounts Intromissions Ejaculations Scr Female 2 Present Copulation Frequency Source: Di Chiara et al. Source: Fiorino and Phillips

18 Effect of Cocaine Abuse on Dopamine D2 Receptors normal subject cocaine abuser (1 month post) cocaine abuser (4 months post)

19 Cocaine Abuse and Brain Glucose Metabolism normal subject cocaine abuser (10 days post) cocaine abuser (100 days post)

20 What is addiction, really? o Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. o It is considered a brain disease because drugs change the brain they change its structure and how it works. These brain changes can be long-lasting, and can lead to the harmful behaviors seen in people who abuse drugs.

21 Treating Substance-Use Disorders Addiction IS a treatable disease. Treatment MUST address the whole person. Simply stopping the use of substances does not equate to recovery.

22 Treating Substance-Use Disorders Treatment must be multidimensional. Harm reduction / Abstinence Behavioral therapies Medication-assisted treatment Self help / Support groups Stable support system Finding meaning/purpose in life Addressing co-occurring mental health issues and other psychosocial stressors Addressing physical health concerns

ine) on (% Baseli Concentratio DA C

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