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

In this study, the mechanism of nicotine‐induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg −1 , s.c.) increased the levels of ACh in hippocampal dialysates. 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) D 1 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.). Local perfusion of mecamylamine (100 μ M ), DHβE (100 μ M ) or SCH‐23390 (10 μ M ) through microdialysis probe did not increase basal hippocampal ACh release. 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 μ M ), but not by MEC (100 μ M ) or DHβE (100 μ M ). Direct perfusion of nicotine (1 m M , but not 0.1 m M ) increased hippocampal ACh levels; however, this effect was relatively insensitive to blockade by co‐perfusion of either mecamylamine (100 μ M ) or SCH‐23390 (10 μ M ). 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.British Journal of Pharmacology (1999) 127 , 1486–1494; doi: 10.1038/sj.bjp.0702683