Neuropharmacology of the Interoceptive Stimulus Properties of Nicotine

Abstract

Preclinical drug discrimination techniques play a significant role in advancing our knowledge of the receptor mechanisms underlying the interoceptive effects of nicotine. Early reports confirmed that nicotinic acetylcholine receptors (nAChRs) are critical for transduction of the nicotine cue. In recent years, advances in molecular biology and the discovery of novel ligands with greater selectively for specific nAChR subtypes have furthered our understanding of these mechanisms. There is now evidence regarding the specific nAChR subtypes involved in nicotine discrimination; in addition, there is also evidence suggesting that other systems (i.e., adenosine, cannabinoid, dopamine, glutamate and serotonin) may play a modulatory role. The neuroanatomical structures mediating the nicotine cue have also begun to be elucidated. However, much remains to be learned about the predictive validity of the drug discrimination procedure, particularly with regard to the relation between interoceptive and reinforcing effects and individual differences in vulnerability to tobacco dependence. Recent data also suggests that the mechanisms involved in the conditional and discriminative stimulus properties of nicotine may be dissociable. Avenues for future research should include assessing the mechanisms of the subjective effects of nicotine withdrawal, factors contributing to individual differences in sensitivity to the nicotine cue, and the role of behavioral factors involved in drug cross-substitution.

Mismatch negativity (MMN) reduction in schizophrenia—Impaired prediction-error generation, estimation or salience?

“…Interestingly, not only do patients show reduced sensitivity to increasing repetition of a new rule , they also failed to show the nicotineinduced enhancement of MMN observed in the control group (Inami et al, 2007, although a very small sample size of n = 10). Nicotine is not a selective acetylcholine agonist so its affect on MMN could also occur via other means (e.g., dopaminergic, serotonergic, and cannabinoid (Herman and Sofuoglu, 2010;Wooters et al, 2009)). In support of this suggestion, a study employing more selective modulation of acetylecholine produced no significant change in MMN (Pekkonen et al, 2005) whilst a recent augmentation of serotonin (5-HT) levels via escitalopram produced a significant increase in MMN amplitude (Wienberg et al, 2010).…”

The effect of sazetidine-A and other nicotinic ligands on nicotine controlled goal-tracking in female and male rats

“…Over the years, a variety of tasks have been developed to study the interoceptive stimulus effects of drugs in rodents and primates (Murray et al , 2011; Stolerman et al , 2009; Wooters et al , 2009). These drug discrimination tasks have served as powerful tools for understanding the behavioral and neuropharmacological processes of psychoactive substances.…”

Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion

“…In the laboratory, human participants will learn to discriminate nicotine from saline and place poker chips in a particular pile when under the influence of nicotine (Perkins et al, 1999). Similarly, rats responding, such as pressing a left lever 25 times to receive a food pellet, will come under the control of the nicotine stimulus (Colpaert, 1999; Solinas et al, 2006; Wooters et al, 2009). These stimulus effects, and the acquired appetitive properties conferred by the learning history, likely contribute to the development of nicotine dependence and the tenacity of habitual tobacco use (Bevins and Palmatier, 2004; Bevins and Murray, 2011).…”