Nicotine-induced enhancement of responding for conditioned reinforcement in rats: role of prior nicotine exposure and α4β2 nicotinic receptors

Abstract

Rationale: Stimuli associated with nicotine can become motivationally significant and may play a role in tobacco dependence. Previous work indicates that nicotine enhances responding for a conditioned reinforcer (CR).

Objectives: These studies examined the effects of prior exposure to nicotine on responding for a CR, persistence of this response, and the role of α4β2 or α7 nicotinic receptor subtypes.

Methods: Water deprived rats were given 13 Pavlovian conditioning sessions where a light/tone conditioned stimulus (CS) was paired with the delivery of water. Then, rats were presented with two levers: one delivered the CS (now a CR), the other was inactive. Experiments examined the effect of nicotine administered prior to Pavlovian conditioning sessions on approach behavior during CS presentations, operant responding for CR in the presence and absence of nicotine, and the persistence of responding for CR. The effects of nicotinic acetylcholine receptor (nAChR) antagonism with mecamylamine and α4β2 or α7 nAChR antagonism with dihydro-beta-erythroidine (DHβE) or methyllycaconitine (MLA) on nicotine-enhanced responding for CR were examined.

Results: Nicotine enhanced approach behavior during CS presentations and potentiated operant responding for CR, an effect sensitized as a result of nicotine exposure during conditioning. Responding for CR and its potentiation by nicotine was stable over multiple tests. Enhanced responding for the CR induced by nicotine was blocked by mecamylamine and DHβE, but not MLA.

Conclusions: Nicotine enhances Pavlovian discriminated approach and shows sensitized nicotine-induced enhancements in responding for CR, an effect depending on α4β2 nAChRs.