Pharmacological Basis for the Tobacco Smoking Habit

Armitage, A. K.; Hall, G. H.; Morrison, Cathleen F.

doi:10.1038/217331a0

Cited by 135 publications

(52 citation statements)

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“…Phasic nicotine injections lead to transient increases in DA levels in the nucleus accumbens and striatum, contingent on nAChR activation (8). Nicotine also affects VTA activity through the GABAergic interneurons (12) that further modify DA signals and may also subserve complementary reward signaling (22).At the behavioral level, long-term smoking has been for a long time considered to be addictive and habit-forming (23)(24)(25). In animal models of smoking, nicotine injection has both motoractivational effects (through the dorsal nigrostriatal pathway) and rewarding effects (through the ventral mesolimbic pathway) (14).…”

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A neurocomputational hypothesis for nicotine addiction

Gutkin

Dehaene

Changeux

2006

Proc. Natl. Acad. Sci. U.S.A.

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We present a hypothetical neurocomputational model that combines a set of neural circuits at the molecular, cellular, and system levels and accounts for several neurobiological and behavioral processes leading to nicotine addiction. We propose that combining changes in the nicotinic receptor response, expressed by mesolimbic dopaminergic neurons, with dopamine-gated learning in action-selection circuits, suffices to capture the acquisition of nicotine addiction. We show that an opponent process enhanced by persistent nicotine-taking renders self-administration rigid and habitual by inhibiting the learning process, resulting in long-term impairments in the absence of the drug. The model implies distinct thresholds on the dosage and duration for the acquisition and persistence of nicotine addiction. Our hypothesis unites a number of prevalent ideas on nicotine action into a coherent formal network for further understanding of compulsive drug addiction.computational model ͉ reward T obacco addiction is a multistage process involving persistent cycles of chronic smoking (1, 2). It is tied to long-lasting effects on mesolimbic dopaminergic (DA) pathways by nicotine, the main addictive substance in tobacco smoke (2, 3). Although the pharmacological target of nicotine is now well identified (4), how nicotine binding translates into addictive behavior remains enigmatic. Particularly puzzling is the ease with which nicotine addiction is acquired and resists despite its limited (or even negative) hedonic impact (3).Both reinforcement learning and opponent processes have been proposed to play a significant role in the development of addiction (5, 6). However, direct DA-dependent reinforcement learning does not conclusively treat the issue of persistence of addictive behaviors to extinction (5), and the opponent process or allostasis (6) theory does not provide a specific computational account of how addiction is acquired. To unravel two such aspects, the acquisition and persistence, we model the interplay between the phasic and the persistent effects of nicotine on the DA pathway and its assumed control of the plasticity in corticostriatal action-selection (A-S) circuits (7). We propose a hypothetical minimal computational circuit of neuronal and pharmacological processes (see Fig. 1) and apply it to a specific animal model of smoking in humans: self-administration of nicotine. Our framework implements the dynamics of interaction between the effect of nicotinic acetylcholine receptors (nAChRs) on the DA neuronal population and learning in a model of A-S. We specify the differential roles of nicotine in the positive (direct) DA response on the acquisition of nicotinetaking and the slow opponent process in its persistence.At the molecular level, nicotine actions are mediated by persistent changes in brain nAChRs involving, among others, the ␤2-subunit (8-11). These nAChRs modulate the excitability of the DA neurons in the ventral tegmental area (VTA) that project to striatal structures (e.g., nucleus accumbens and striatum) ...

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“…At the behavioral level, long-term smoking has been for a long time considered to be addictive and habit-forming (23)(24)(25). In animal models of smoking, nicotine injection has both motoractivational effects (through the dorsal nigrostriatal pathway) and rewarding effects (through the ventral mesolimbic pathway) (14).…”

mentioning

confidence: 99%

A neurocomputational hypothesis for nicotine addiction

Gutkin

Dehaene

Changeux

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…These effects are overshadowed by the propensity of nicotine to release catecholamines from the adrenal medulla and other sites. It depresses spinal reflexes, excites respiration through stimulation of the carotid body, and activates the electroencephalogram (Armitage, Hall & Morrison, 1968). Cigarette smoking replicates all these actions.…”

Section: Nicotine and Smoking Behaviourmentioning

confidence: 99%

Nicotine and Smoking Behaviour

Lader¹

1978

Brit J Clinical Pharma

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“…Subjective evidence is offered by smokers, who claim to feel tranquillized or stimulated after smoking a cigarette and there is pharmacological evidence that changes in motor activity and electroencephalogram recordings which follow the administration of nicotine to rats, may be interpreted as being consistent with these claims in man (Armitage, Hall and Morrison, 1968).…”

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A Study of the Effects of Altering the Tar/Nicotine Ratio in Experimental Tobacco Carcinogenesis

Davies¹,

Whitehead²

1970

Br J Cancer

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SUMMARY.-There was no statistically significant difference in specific mouse skin carcinogenicity between smoke condensate from plain, flue-cured tobacco cigarettes with a normal tar to nicotine ratio and condensate from filter-tip cigarettes made from selected flue-cured tobaccos with a reduced tar to nicotine ratio.NUMEROUS mouse skin painting experiments with tobacco smoke condensate have repeatedly demonstrated a relationship between weight of condensate applied and the tumour response (Wynder et al., 1953;Day, 1967). This observation is consistent with conclusions reached from human epidemiological evidence that the risk of developing lung cancer increases with the duration of smoking and the number of cigarettes smoked per day (Best, Josie and Walker, 1960; Doll and Hill, 1954, 1956). If this risk is associated wholly with the particulate phase of smoke, although at present there is no evidence to support this belief, then reduction in the tar and nicotine yields of cigarettes would be desirable and can be achieved by the use of an efficient filter. Such reductions would only be useful provided the smoker did not increase his daily consumption of these cigarettes, or change his smoking habits in order, possibly, to restore his intake of nicotine to the level to which he had become accustomed.It is believed that, particularly in the inhaling tobacco smoker, nicotine plays an important role, although the mode of action remains unknown. Subjective evidence is offered by smokers, who claim to feel tranquillized or stimulated after smoking a cigarette and there is pharmacological evidence that changes in motor activity and electroencephalogram recordings which follow the administration of nicotine to rats, may be interpreted as being consistent with these claims in man (Armitage, Hall and Morrison, 1968).It is possible by a combination of selected tobacco blends and a filter to produce cigarette smoke with a satisfactory nicotine content to the smoker but with a reduced tar yield, which would fulfil the objectives mentioned earlier, provided that its carcinogenicity was not increased.The work now reported was undertaken to determine whether there was any significant difference in specific mouse skin carcinogenicity between flue-curedt * The term " tar " is used in this paper as an alternative to the more scientifically correct term "total particulate matter ." t Flue-cured refers to an example of a method of curing tobacco leaf. The leaves are hung in wholly enclosed barns. The curing process is carried out by conveying heat through sheet-iron flues running across the floor. No smoke comes into contact with the leaves. The process takes about 4 days and the doors of the barns are then opened and the cured leaf is allowed to soften by absorbing moisture from the atmosphere. R. F. DAVIES AND J. K. WHITEHEAD cigarette smoke condensate with the normal tar to nicotine ratio and condensate with a reduced tar to nicotine ratio. The latter condensate was obtained from cigarettes made of selected tobaccos carefully ble...

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Pharmacological Basis for the Tobacco Smoking Habit

Cited by 135 publications

References 9 publications

A neurocomputational hypothesis for nicotine addiction

A neurocomputational hypothesis for nicotine addiction

Nicotine and Smoking Behaviour

A Study of the Effects of Altering the Tar/Nicotine Ratio in Experimental Tobacco Carcinogenesis

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