Disentangling the nature of the nicotine stimulus

Abstract

Learning involving interoceptive stimuli likely plays an important role in many diseases and psychopathologies. Within this area, there has been extensive research investigating the interoceptive stimulus effects of abused drugs. In this pursuit, behavioral pharmacologists have taken advantage of what is known about learning processes and adapted the techniques to investigate the behavioral and receptor mechanisms of drug stimuli. Of particular interest is the nicotine stimulus and the use of the two-lever operant drug discrimination task and the Pavlovian drug discriminated goal-tracking task. There is strong concordance between the two methods when using “standard” testing protocols that minimize learning on test days. For example, ABT-418, nornicotine, and varenicline all fully evoked nicotine-appropriate responding. Notably, research from our laboratory with the discriminated goal-tracking task has used an alternative testing protocol. This protocol assesses stimulus substitution based on how well extinction learning using a non-nicotine ligand transfers back to the nicotine stimulus. These findings challenge conclusions based on more “standard” testing procedures (e.g., ABT-418 is not nicotine-like). As a starting point, we propose Thurstone scaling as a quantitative method for more precisely comparing transfer of extinction across doses, experiments, and investigators. We close with a discussion of future research directions and potential implications of the research for understanding interoceptive stimuli.

Interoceptive conditioning with the nicotine stimulus

“…In summation, different approaches to assessing interoceptive conditioning and the similarity of ligands or doses of a ligand can sometimes lead to different conclusions (see also Kaempf and Kallman, 1987;Reichel et al, 2010;Bevins et al, 2012). One advantage of the repeated extinction and the transfer of extinction protocols revealed in the present research was that doses traditionally producing motor impairment could be evaluated.…”

“…Exposure to repeated extinction sessions following administration of varenicline or nornicotine produced diminished responding to nicotine; administration of ABT-418 had no effect on responding. We have come to refer to this generalization of extinction effect as 'transfer of extinction learning' (Reichel et al, 2010;Bevins et al, 2012).…”

“…Behavioral and neurobiological research has provided copious evidence that extinction is a new form of learning that counteracts or interferes with the expression of the previously learned conditioned response (CR) (Pavlov, 1927;Konorski, 1948;Bouton, 1991;Bouton, 1993;Rescorla, 1997;Bevins et al, 1999;Rauhut et al, 2001;Rescorla, 2001;Bouton, 2002;Davis and Myers, 2002;Delamater, 2004;Quirk and Mueller, 2008). Reichel et al (2010) took this notion that attenuated responding in extinction is new competing learning and assessed whether expression of interoceptive conditioning with nicotine could be weakened if extinction was conducted with a ligand that shared stimulus effects with nicotine (see also Bevins et al, 2012). To this end, Reichel et al (2010) used ABT-418, nornicotine, and varenicline as the ligands to replace nicotine in extinction.…”

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

“…Their control of behavior can be modified by experiences (i.e., learning processes). This learning regarding interoceptive stimuli is involved in such important health issues as pain, aging and cognition, eating disorders (Craig, 2003; Kanoski, 2012), and drug addiction (Bevins and Palmatier, 2004; Bevins et al, 2012). We have been using the discriminated goal-tracking task to study the behavioral and neural processes of interoceptive conditioning involving the nicotine stimulus (Bevins and Murray, 2011; Bevins et al, 2012; Charntikov et al, 2012).…”

“…This learning regarding interoceptive stimuli is involved in such important health issues as pain, aging and cognition, eating disorders (Craig, 2003; Kanoski, 2012), and drug addiction (Bevins and Palmatier, 2004; Bevins et al, 2012). We have been using the discriminated goal-tracking task to study the behavioral and neural processes of interoceptive conditioning involving the nicotine stimulus (Bevins and Murray, 2011; Bevins et al, 2012; Charntikov et al, 2012). The research in the present report extends previous studies showing bupropion substitution for the interoceptive stimulus effects of nicotine (Besheer et al, 2004; Wiley et al, 2002; Wilkinson et al, 2010; Young and Glennon, 2002).…”