Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues.

Rationale: We recently demonstrated that blocking specific nicotinic acetylcholine receptors (nAChRs) abolishes the conditioned reinforcing properties of ethanol-associated cues in rat, suggesting nAChRs as promising pharmacological targets for prevention of cue-induced relapse.

Objectives: The present study investigated the involvement of nAChR subtypes in the conditioned reinforcing properties of stimuli associated with a natural reward (sucrose).

Methods: Water-deprived rats were trained to associate a tone + light stimulus (CS) with the presentation of a 0.1 M sucrose solution for 10 consecutive days. On the subsequent day, the animals were tested on the stringent acquisition of a new instrumental response with conditioned reinforcement, following a systemic injection of the nonselective nAChR antagonist mecamylamine (MEC) or the selective α7 and α6/α3β2β3* nAChR antagonist methyllycaconitine (MLA). At testing, the rats were presented with two novel levers. Responding on the lever assigned as active (CR lever) resulted in a presentation of the CS alone, while pressing the inactive lever (NCR lever) had no programmed consequences.

Results: Control animals pressed the CR lever significantly more than the NCR lever, demonstrating that the CR had acquired conditioned reinforcing properties. Systemic MEC as well as MLA reduced the CR lever responses to the same level as for the NCR lever.

Conclusions: These results demonstrate a role for the α7 and/or α6/α3β2β3* nAChRs in conditioned reinforcement to a natural reward and suggest neuronal nAChRs as common mediators of the impact of cues on incentive processes.