Pharmacological characterization of nicotine-induced acetylcholine releasein the rat hippocampus in vivo: evidence for a permissive dopamine synapse

1 In this study, the mechanism of nicotine-induced hippocampal acetylcholin e (ACh) release in awake, freely moving rats was examined using in vivo mic rodialysis. 2 Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the l evels of ACh in hippocampal dialysates. 3 The nicotine-induced hippocampal ACh release was sensitive to the pretrea tment of neuronal nicotinic acetylcholine receptor (nAChR) antagonists meca mylamine (3.0 mg kg(-1), s.c.) and dihydro-beta-erythrodine (DH beta E; 4.0 mg kg(-1), s.c.) as well as systemic administration of the dopamine (DA) D -1 receptor antagonist SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-pheny l-2,3,4,5-tetrahydro-1H-benzazepine; 0.3 mg kg(-1), s.c.). 4 Local perfusion of mecamylamine (100 mu M), DH beta E (100 mu M) or SCH-2 3390 (10 mu M) through microdialysis probe did not increase basal hippocamp al ACh release. 5 Hippocampal ACh release elicited by systemic administration of nicotine ( 0.4 mg kg(-1), s.c.) was antagonized by local perfusion of SCH-23390 (10 mu M), but not by MEC (100 mu M) or DH beta E (100 mu M). 6 Direct perfusion of nicotine (1 mM, but not 0.1 mM) increased hippocampal ACh levels; however, this effect was relatively insensitive to blockade by co-perfusion of either mecamylamine (100 mu M) Or SCH-23390 (10 mu M). 7 These results suggest that nicotine-induced hippocampal ACh release occur s by two distinct mechanisms: (1) activation of nAChRs outside the hippocam pus leading to DA release and subsequent ACh release involving a permissive DA synapse, and (2) direct action of nicotine within the hippocampus leadi ng to ACh release via non-DA-ergic mechanism.