Hippocampal alpha4beta2 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 microg 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 alpha4beta2 nAChR antagonist, dihydro-beta-erythroidine (DHbetaE) (6.00 and 18.00 microg per side), or the preferential alpha7 nAChR antagonist, methyllycaconitine (MLA) (13.50 and 27.00 microg per side), was bilaterally infused into the dorsal hippocampus before systemic injections of nicotine (0.09 mg/kg). DHbetaE infusions dose-dependently blocked the enhancement of contextual fear conditioning by nicotine, whereas MLA infusions yielded an intermediate effect. In addition, neither DHbetaE nor MLA had an effect on contextual fear conditioning in the absence of systemic nicotine. The present results suggest a critical role for alpha4beta2 nAChRs in the dorsal hippocampus for mediating the enhancing effect of nicotine on contextual fear conditioning.