Acute and chronic nicotine exposure differentially facilitate the induction of long-term potentiation (LTP), a synaptic model of learning and memory, in the hippocampal CA1 region. The mechanisms underlying these effects of nicotine, however, are unknown. In the present study, both nicotinic acetylcholine receptor (nAChR) agonists and an alpha 7 nAChR antagonist facilitated the induction LTP in the hippocampal CA1 region of naive rat. Furthermore, chronic nicotine treatment lowered the threshold for induction of LTP, and acute application of nicotinic agonists, but not an alpha 7 antagonist, further facilitated LTP induction in the chronic-nicotine-treated hippocampus. These results suggest not only that both activation of non-alpha 7 nAChRs and inactivation of alpha 7 nAChRs contribute to LTP induction, but also that chronic-nicotine-mediated facilitation of LTP induction is due to chronic-nicotine-induced desensitization of alpha 7 nAChRs, (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.