Nicotine and behavioral sensitization.

Department of Anesthesia and Critical Care, University of Chicago, MC4028, Chicago, IL 60637, USA.
Journal of Molecular Neuroscience (Impact Factor: 2.76). 09/2009; 40(1-2):154-63. DOI: 10.1007/s12031-009-9230-7
Source: PubMed

ABSTRACT Use of tobacco products contributes to hundreds of thousands of premature deaths and untold millions of dollars in health care costs in this country each year. Nicotine is the principal neuroactive component in tobacco, but, despite ongoing research efforts, the cellular basis of its effects on behavior remains unclear. Efforts to resolve this conundrum have focused on the mesoaccumbens dopamine system, which contributes to the rewarding effects of many addictive drugs, including nicotine. The goal of this review is to outline recent advances and highlight some of the important unanswered questions regarding nicotine's effects on neuronal excitability and synaptic plasticity within the brain reward pathways.

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    ABSTRACT: Abstract It is well established that the reinforcing properties of nicotine (NIC) depend on its action on nicotinic acetylcholine receptors expressed by brain neurons. However, when administered systemically, NIC first phasically activates nicotinic receptors located on the afferents of sensory nerves at the sites of drug administration before reaching the brain and directly interacting with central neurons. While this peripheral action of NIC has been known for years, it is usually neglected in any consideration of the drug's reinforcing properties and experience-dependent changes of its behavioral and physiological effects. The goal of this work was to review our recent behavioral, electrophysiological, and physiological data suggesting the critical importance of peripheral actions of NIC in mediating its neural effects following acute drug exposure and their involvement in alterations of NIC effects consistently occurring following repeated drug exposure. Because NIC, by acting peripherally, produces a rapid sensory signal to the central nervous system that is followed by slower, more prolonged direct drug actions in the brain, these two pharmacological actions interact in the central nervous system during repeated drug use with the development of Pavlovian conditioned association. This within-drug conditioning mechanism could explain the experience-dependent changes in the physiological, behavioral, and human psychoemotional effects of NIC, which, in drug-experienced individuals, always represent a combination of pharmacological and learning variables.
    Reviews in the neurosciences 02/2014; 25(2). DOI:10.1515/revneuro-2013-0067 · 3.31 Impact Factor
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    ABSTRACT: Stress enhances the locomotor stimulant and discriminative stimulus effects of several addictive drugs (e.g., morphine) in rodents, yet interactions between stress and nicotine's effects in these behavioral models have not been well established. To this end, the current studies examined the effects of restraint stress on nicotine-induced locomotor activity and nicotine discrimination in rats. We used a novel approach in which onset of stress and nicotine administration occurred concurrently (i.e., simultaneous exposure) to simulate effects of stress on ongoing tobacco use, as well as a more traditional approach in which a delay was imposed between stress and nicotine administration (i.e., sequential exposure). Simultaneous exposure to stress reduced the rate of locomotor sensitization induced by daily injections of nicotine (0.4mg/kg, s.c.). A lower dose of nicotine (0.1mg/kg, s.c.) produced modest effects on activity that were generally unaffected by simultaneous exposure to stress. Sequential exposure to stress and nicotine (0.4mg/kg, s.c.) slightly suppressed nicotine-induced activity, but did not influence rate of locomotor sensitization. Neither simultaneous nor sequential exposure to stress influenced the discriminative stimulus effects of nicotine (0.01 - 0.2mg/kg, s.c.). These data show that restraint stress reduces nicotine's locomotor stimulant effects, particularly when onset of stress and nicotine exposure occurs simultaneously, but does not influence nicotine discrimination. These findings contrast with the ability of stress to enhance the effects of other drugs in these models. This study also suggests that studying the influence of simultaneous stress exposure on drug effects may be useful for understanding the role of stress in addiction.
    Pharmacology Biochemistry and Behavior 05/2014; DOI:10.1016/j.pbb.2014.05.012 · 2.82 Impact Factor
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    ABSTRACT: The mesocorticolimbic system plays a central role in nicotine dependence and withdrawal.•It consists of multiple functionally distinct pathways that mediate distinct aspects of nicotine reinforcement and aversion.•The acute and chronic effects of nicotine are mainly mediated by nicotinic, dopaminergic, and glutamatergic transmission in mesocorticolimbic circuits.
    Progress in Neurobiology 11/2014; DOI:10.1016/j.pneurobio.2014.10.002 · 10.30 Impact Factor


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