Received for publication December 5, 2003.
Revised February 2, 2004.
Accepted for publication February 6, 2004.

Effects of galantamine, a nicotinic allosteric potentiating ligand, on nicotine-induced catecholamine release in hippocampus and nucleus accumbens of rats

Abstract

Galantamine, a drug for treatment of Alzheimer's disease, is a novel cholinergic agent with a dual mode of action that inhibits acetylcholinesterase and allosterically modulates nicotinic cholinergic receptors (nAChRs). Nicotine stimulates catecholamine secretion, inducing hippocampal norepinephrine (NE) release, and improves memory consolidation. Thus, the effect of galantamine on nicotine-induced hippocampal NE secretion was investigated. This was compared with the effect of galantamine on nicotine-induced DA release within the nucleus accumbens of the same rat. Nicotine (0.025-0.09 mg/kg; i.v.) dose-dependently increased NE and DA levels in microdialysates from the hippocampus and nucleus accumbens, respectively, of freely moving rats. Pretreatment with galantamine (3.0 mg/kg, s.c.) 3 h prior to nicotine either potentiated NE responses to doses of nicotine that were ineffective alone (0.025-0.045 mg/kg) or significantly enhanced (0.065 mg/kg) NE responses, whereas galantamine was ineffective when administered 2 or 4 h before nicotine. In contrast to its effects on NE, galantamine did not alter accumbal DA responses to any dose of nicotine. These selective effects of galantamine on nicotine-stimulated NE secretion may reflect differences in local neural circuits that utilize nAChRs to modulate hippocampal NE versus accumbal DA release.

Key words: Dopamine, Galantamine, Hippocampus, Microdialysis, Nicotine, Norepinephrine