Article date: July 1999
By: Richard T Reid, G Kenneth Lloyd, Tadimeti S Rao, in Volume 127, Issue 6, pages 1486-1494
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) 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.).
Local perfusion of mecamylamine (100 μM), DHβE (100 μM) or SCH‐23390 (10 μM) 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 μM), but not by MEC (100 μM) or DHβE (100 μM).
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).
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.
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) 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.).
Local perfusion of mecamylamine (100 μM), DHβE (100 μM) or SCH‐23390 (10 μM) 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 μM), but not by MEC (100 μM) or DHβE (100 μM).
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).
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
DOI: 10.1038/sj.bjp.0702683
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