The importance of acquisition learning on nicotine and varenicline drug substitution in a drug-discriminated goal-tracking task

Thompson, Brady M.; Barrett, Scott T.; Huynh, Y. Wendy; Kwan, David A.; Murray, Jennifer E.; Bevins, Rick A.

doi:10.1016/j.pbb.2020.173045

Cited by 4 publications

(4 citation statements)

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“…The initial objective of this study was to determine whether varenicline would serve as the training stimulus in the DGT task. In a set of earlier studies, we found that 1 mg/kg varenicline seamlessly replaced the control of acquired goal-tracking behavior in rats when 0.4 mg/kg nicotine initially served as the training stimulus (Thompson et al, 2019, 2020); an outcome suggesting that varenicline might serve as a training stimulus in the DGT task. The present study confirmed that possibility.…”

Section: Discussionmentioning

confidence: 87%

“…30 varenicline and 30 saline sessions) to ensure goal-tracking rates were stable before moving to the testing phase. The timing of the varenicline injection relative to the start of the session, as well as the training dose of varenicline, was based on Thompson et al, (2019Thompson et al, ( , 2020.…”

Section: Discrimination Trainingmentioning

confidence: 99%

“…Of particular interest in the present report is the research on the partial α 4 β 2 nicotinic acetylcholine receptor (nAChR) agonist varenicline (Rollema et al , 2007), marketed in the USA as the smoking cessation aid Chantix. In rats initially trained to discriminate between nicotine and saline, varenicline in substitution tests partially to fully evoke nicotine-like responding (Smith et al , 2007; LeSage et al , 2009; Reichel et al , 2010; Thompson et al , 2020). Similarly, in previous work from our lab, Thompson et al , (2019) trained rats to discriminate the nicotine (0.4 mg/kg) stimulus from saline in the DGT task, where nicotine served as the interoceptive stimulus for brief intermittent access to sucrose.…”

Section: Introductionmentioning

confidence: 99%

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Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

Thompson

Tracy

Huynh

et al. 2022

Behavioural Pharmacology

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Varenicline (Chantix) is an FDA-approved smoking cessation aid that is pharmacologically similar to nicotine, the primary addictive component found within tobacco. In support of this similarity, previous drug discrimination research in rats has reported that the internal or interoceptive stimulus effects of nicotine and varenicline share stimulus elements. Those shared elements appear to be mediated, in part, by overlapping action at alpha4beta2–containing nicotinic acetylcholine receptors (nAChRs). The research supporting this conclusion, however, has only used nicotine, and not varenicline, as the training drug. Accordingly, we used the discriminated goal tracking (DGT) task in which 1 mg/kg varenicline signaled intermittent access to sucrose. On separate intermixed saline days, sucrose was not available. Rats acquired the discrimination as measured by a differential increase in dipper entries (goal tracking) evoked by varenicline. These rats then received a series of tests with several doses of varenicline, nicotine, nornicotine (a metabolite of nicotine and tobacco alkaloid), sazetidine-A (a partial alpha4beta2 agonist), PHA-543613 (an alpha7 agonist), and bupropion (a norepinephrine and dopamine reuptake inhibitor). Control of goal tracking by varenicline was dose-dependent. Nicotine and nornicotine evoked responding comparable to the varenicline training dose indicating full substitution. Sazetidine-A partially substituted for the varenicline stimulus, whereas bupropion and PHA-543613 evoked little to no varenicline-like responding. These findings indicate that varenicline can serve as the training stimulus in the DGT task. Further, stimulus control of varenicline in the DGT task is driven by its partial agonist activity at alpha4beta2–containing nAChRs. The use of this approach could lead to a better understanding of the pharmacological action of varenicline and help guide treatment geared towards tobacco cessation through a more targeted development of novel synthetically designed, subunit-specific pharmacological interventions.

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Section: Discussionmentioning

confidence: 87%

Section: Discrimination Trainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

Thompson

Tracy

Huynh

et al. 2022

Behavioural Pharmacology

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“…For over 18 years, we have demonstrated that nicotine produces distinct stimulus effects that can form behaviorally relevant associations with appetitive reinforcing stimuli, and that these associations operate according to the general principles of Pavlovian learning (Besheer et al, 2004;Bevins et al, 2012;Murray & Bevins, 2009;Thompson et al, 2020). Briefly, the general design of these studies involves injecting food-restricted rats subcutaneously with either nicotine (0.4 mg/kg is a typical dose) or saline vehicle before exposing them to a 20-min conditioning session.…”

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confidence: 99%

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Barrett

Flynn

Huynh

et al. 2022

J Exper Analysis Behavior

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Nicotine produces robust stimulus effects that can be conditioned to exert stimulus control over behavior through associative learning. Additionally, nicotine has weak reinforcing effects that are inconsistent with its prevalence of use and the tenacity of nicotine dependence. The present study investigated whether conditioned associations to the nicotine drug stimulus may confer additional reinforcing strength to nicotine that thereby increase its use liability, and presents a new methodological approach to investigating the interaction between the stimulus effects and reinforcing effects of drugs. Male and female Sprague–Dawley rats were divided into groups receiving intravenous infusions of either 0.03 mg/kg nicotine or 0.9% saline that were either Paired (30 s delayed) or explicitly Unpaired (4 to 6 min delayed) with sucrose deliveries over 24 daily conditioning sessions. Thereafter, recessed nosepoke response devices were installed in the chambers and infusions of their assigned drug solutions were contingently available according to a progressive ratio schedule. Rats in the Paired Nicotine condition acquired the nosepoke response, expressed active nosepoke discrimination, and self‐administered significantly more infusions than rats in any of the other groups. These results demonstrate that the interoceptive stimulus effects of nicotine can form Pavlovian associations with reinforcing events that alter its reinforcement efficacy.

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Disruption of positive- and negative-feature morphine interoceptive occasion setters by dopamine receptor agonism and antagonism in male and female rats

Peart,

Nolan,

Stone

et al. 2024

Psychopharmacology

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The importance of acquisition learning on nicotine and varenicline drug substitution in a drug-discriminated goal-tracking task

Cited by 4 publications

References 32 publications

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Disruption of positive- and negative-feature morphine interoceptive occasion setters by dopamine receptor agonism and antagonism in male and female rats

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