Rochford_1996_J.Pharmacol.Exp.Ther_277_1267

The present experiments assessed the influence of nicotinic cholinergic receptors on latent inhibition (LI), which is the decrement in Pavlovian conditioning resulting from extensive preexposure to a conditioned stimulus (CS). LI was assessed within a conditioned emotional response paradigm involving three phases: preexposure [either 0 (nonpreexposed) or 60 (preexposed) presentations of a 60 sec tone], conditioning (two-tone, 0.6 mA; 0.5-sec footshock pairings) and test (assessment of CS-induced suppression of lever press responding). LI was obtained in that untreated preexposed-animals displayed less conditioned suppression compared to nonpreexposed controls. Administration of nicotine (0.4 mg/kg i.p.) augmented LI when administered during conditioning. In addition, nicotine enhanced LI when administered during preexposure, suggesting that nicotine can enhance the ability of an animal to filter irrelevant stimuli. The nicotinic agonists cytisine (5 mg/kg) and lobeline (10 mg/kg) also augmented LI. Nicotine did not influence the behavior of nonpreexposed animals, suggesting that nicotine's effect was specific to mechanisms mediating LI. The nicotinic antagonists hexamethonium (10 mg/kg) and mecamylamine (5 mg/kg) reversed nicotine's enhancement of LI. Finally, nicotine's effect on LI was found to depend upon CS preexposure parameters; nicotine attenuated, rather than enhanced, the LI observed after 40 presentations of a 5-sec CS. These results suggest that stimulation of nicotine receptors can either amplify or curtail the efficacy of mechanisms involved in filtering irrelevant stimuli from further cognitive processing and that the direction of this modulation depends on the CS preexposure parameters.