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

Abstract

1. In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. 2. Systemic administration of nicotine (0.4 mg kg-1, s.c.) increased the levels of ACh in hippocampal dialysates. 3. The nicotine-induced hippocampal ACh release was sensitive to the pretreatment of neuronal nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine (3.0 mg kg-1, s.c.) and dihydro-β-erythrodine (DHβE; 4.0 mg kg-1 s.c.) as well as systemic administration of the dopamine (DA) D1 receptor antagonist SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine; 0.3 mg kg-1, s.c.). 4 .Local perfusion of mecamylamine (100 μM), DHβE (100 μM) or SCH-23390 (10 μM) through microdialysis probe did not increase basal hippocampal 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 μM), but not by MEC (100 μM) or DHβE (100 μM). 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 μM) or SCH-23390 (10 μM). 7. These results suggest that nicotine-induced hippocampal ACh release occurs by two distinct mechanisms: (1) activation of nAChRs outside the hippocampus leading to DA release and subsequent ACh release involving a permissive DA synapse, and (2) direct action of nicotine within the hippocampus leading to ACh release via non-DA-ergic mechanism.