Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers |
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Authors: | Deon?M?Harvey Sevil?Yasar Stephen?J?Heishman Leigh?V?Panlilio Jack?E?Henningfield Email author" target="_blank">Steven?R?GoldbergEmail author |
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Institution: | (1) Clinical Pharmacology and Therapeutics Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, Md., USA;(2) Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA;(3) Behavioral Neurosciences Section, National Institute on Drug Abuse, NIH, DHHS, Baltimore, Md., USA;(4) Preclinical Pharmacology Section, National Institute on Drug Abuse, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA;(5) Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA;(6) Pinney Associates, Bethesda, Md., USA |
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Abstract: | Rationale Although numerous studies have documented that nicotine can function as an effective reinforcer of intravenous self-administration behavior in animals, it has not been clearly shown to maintain intravenous self-administration behavior above vehicle placebo levels in humans.Objectives To compare the reinforcing effectiveness of nicotine versus saline placebo in human research volunteers responding under fixed-ratio (FR) schedules of intravenous drug self-administration while systematically increasing response requirements.Methods Eight male cigarette smokers resided in an inpatient research unit. During 3-h sessions, intravenous injections of nicotine and saline were available concurrently and were contingent on responding (pulling a lever). Nicotine dose (0.75, 1.5, 3.0 mg/injection), time out (TO) value after each injection (1–20 min) and FR response requirement (10–1600) were varied in different subjects over consecutive sessions.Results Number of nicotine injections/session significantly decreased as dose/injection increased and the number of self-administered nicotine injections was significantly greater than the number of self-administered saline injections across conditions. When FR value was progressively increased over sessions, response rates for nicotine, but not saline, injections increased, with maximal rates at the highest FR values. Rates of responding and injections/session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above. Subjects rated effects of nicotine as both significantly more positive and more negative than saline placebo, with positive ratings significantly higher than negative ratings.Conclusions Nicotine functioned as a prototypic drug of abuse, serving as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Subjects adjusted their responding to response requirements in a way that maintained relatively constant levels of nicotine injections per session.Abstracts of these experiments previously appeared in Pharmacologist 25:219, 1983, and Neurosci Lett 14(Suppl):140, 1983. |
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Keywords: | Nicotine Human Tobacco smoking behavior Drug self-administration Intravenous Fixed-ratio schedule |
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