Hippocampal α4β2 nicotinic acetylcholine receptor involvement in the enhancing effect of acute nicotine on contextual fear conditioning

Nicotine is known to enhance learning and memory in hippocampus-dependent tasks such as contextual fear conditioning. The present study was designed to directly examine whether the hippocampus plays a role in mediating this enhancement and which nicotinic acetylcholine receptor ( nAChR) subtypes localized to the hippocampus are critical for enhanced learning. Contextual fear conditioning consisted of two white noise conditioned stimuli presentations, each coterminating with a 2 s, 0.57 mA footshock separated by a 120 s intertrial interval. Nicotine ( 0.09, 0.18, and 0.35 mu g per side) was bilaterally infused into the dorsal hippocampus before training and testing. Infusions of nicotine into the dorsal hippocampus produced a dose-dependent enhancement of contextual fear conditioning. To determine which nAChRs are critical to the enhancing effect of nicotine, the preferential alpha 4 beta 2 nAChR antagonist, dihydro-beta-erythroidine ( DH beta E) ( 6.00 and 18.00 mu g per side), or the preferential alpha 7 nAChR antagonist, methyllycaconitine ( MLA) ( 13.50 and 27.00 mu g per side), was bilaterally infused into the dorsal hippocampus before systemic injections of nicotine ( 0.09 mg/kg). DH beta E infusions dose-dependently blocked the enhancement of contextual fear conditioning by nicotine, whereas MLA infusions yielded an intermediate effect. In addition, neither DH beta E nor MLA had an effect on contextual fear conditioning in the absence of systemic nicotine. The present results suggest a critical role for alpha 4 beta 2 nAChRs in the dorsal hippocampus for mediating the enhancing effect of nicotine on contextual fear conditioning.