- Mecamylamine selectively reduced No-Go active responses, decreasing percent No-Go responses and indicating reduced impulsive action during nicotine self-administration.
- Nicotine and varenicline reduced active responding in both Go and No-Go periods, reflecting nonspecific response suppression rather than altered impulsive action.
- Go/No-Go nicotine self-administration task effectively isolates nAChR-dependent modulation of impulsive action; no sex differences observed.
Front Pharmacol. 2026 Sep 21;17:1883945. doi: 10.3389/fphar.2026.1883945. eCollection 2026.
ABSTRACT
INTRODUCTION: Tobacco use disorder is a chronic condition characterized by compulsive nicotine use, withdrawal, and relapse following abstinence. Impulsivity contributes to persistent nicotine use and poor cessation outcomes. This study examined whether nicotinic acetylcholine receptor (nAChR) modulators alter impulsive action in a nicotine self-administration Go/No-Go task in male and female rats.
METHODS: Rats acquired intravenous nicotine self-administration and were then trained in a Go/No-Go procedure in which active lever presses were reinforced during Go periods but not during No-Go periods. Impulsive action was quantified as the percentage of active lever responses during No-Go periods relative to total active responses. We then assessed the effects of varenicline (0.1-3 mg/kg), nicotine (0.1-0.6 mg/kg), and the nAChR antagonist mecamylamine (0.5-2 mg/kg) in the Go/No-Go procedure.
RESULTS: Varenicline and nicotine pretreatment reduced active responding during both Go and No-Go periods, whereas mecamylamine selectively reduced responding during No-Go periods. Mecamylamine decreased the percentage of active responses during No-Go trials, indicating reduced impulsive action during nicotine self-administration. In contrast, nicotine and varenicline did not alter response allocation, suggesting that their effects reflected nonspecific reductions in responding rather than changes in impulsive action. No sex differences were observed. Substituting saline for nicotine during self-administration did not alter active responding during Go periods, but rats in the saline group had fewer active responses during No-Go periods than rats in the nicotine group.
DISCUSSION: These results demonstrate differential effects of nAChR modulators on impulsive action during nicotine self-administration. This work supports the utility of Go/No-Go self-administration task for investigating nAChR-dependent modulation of impulsive action during nicotine self-administration.
PMID:42835367 | PMC:PMC13635303 | DOI:10.3389/fphar.2026.1883945
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