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Biobehavioral Determinants of Smoking

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Biobehavioral Determinants of Smoking

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    1. Biobehavioral Determinants of Smoking Eric Donny, Ph.D. Assistant Professor Department of Psychology University of Pittsburgh

    3. Primary psychoactive ingredient in tobacco smoke Rapidly absorbed from the lungs and delivered to the brain Activates nicotinic acetylcholine receptors (nAChR) Increased activity in the mesolimbic dopamine system Produces robust reinforcing effects Chronic use produces neuroadaptations heightened reinforcing/incentive motivational effects of nicotine and/or withdrawal symptoms during abstinence from nicotine

    4. Today�s talk Some challenges for this model Some additional features of nicotine and tobacco use that need to be considered

    5. Other psychoactive components MAO � enzyme that breaks down monoamines including dopamine Smokers have reduced MAO, an effect attributed to a non-nicotine pharmacological action of tobacco

    6. Absorption of nicotine by the lungs

    7. Nicotine Activates Nicotinic Receptors Nicotinic Receptor Structure

    8. Nicotine Activates Nicotinic Receptors Distribution

    9. Exposure to nicotine leads to a short-lived (desensitization) or prolonged (inactivation) loss of function of the nAChR Differs by receptor subtype a4�2 desensitizes rapidly Some subtypes (e.g., a7) are much less affected Nicotine Activates Nicotinic Receptors Desensitization and Inactivation

    10. Long term exposure to nicotine increases the number of nAChR Differs by subtype ?4�2 upregulated substantially Some subtypes may not be affected May be a response to desensitization Nicotine Activates Nicotinic Receptors Upregulation

    11. Nicotine activates dopamine Lesions of the mesolimbic dopamine pathway dramatically reduce nicotine self-administration (Corrigall et al., 1992) Nicotine administration increase dopamine overflow in the nucleus accumbens However, the effects of nicotine on dopamine change with repeated exposure Attenuation of dopamine release in the nucleus accumbens shell Increase in dopamine release in the nucleus accumbens core Other neurotransmitter systems (e.g., glutamate, GABA, NE, 5-HT) may also important

    13. Why do people smoke? Nicotine 4000 non-nicotine constituents Multiple environmental stimuli, including the sight, smell, and taste of cigarette smoke, the oropharyngeal consequences of smoking, and external contextual stimuli that are normally associated with the behavior

    14. Smoking Stimuli Cues for smoking Conditioned reinforcers

    15. Smoking Stimuli Cynthia Conklin (personal communication) CONTEXTS SMOKING bus stop restaurant Bar NON-SMOKING church gym shower PROXIMAL SMOKING cigarette & ashtray lighters pack of cigarettes NON-SMOKING pen & pad chapstick bar of soap

    19. Smoking Stimuli Exposure to smoking stimuli and/or the act of smoking may also serve as a trigger for subsequent smoking

    20. Smoking Stimuli Experimental model of abstinence and relapse (Juliano et al., 2006) Days 1-4: required abstinence ($80) Day 4: random assignment No smoking Smoke nicotine-containing cigarettes Smoke de-nicotinized cigarettes Days 5-10: abstinence/relapse test $12, $12, $9, $9, $6, $6

    21. Smoking Stimuli

    22. Smoking Stimuli Cues for smoking Conditioned reinforcers

    23. Unrestricted Smoking Cigarettes per day

    25. Conclusions The biological and behavioral determinants of smoking are quite complex Individual differences in these factors may help explain risk for use and/or dependence Interventions should consider both pharmacological and behavioral influences if they are to be maximally effective

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