Jpn. J. Pharmacol. 84 (2), 163-173 (2000)

The Scopolamine-Induced Impairment of Spatial Cognition Parallels the Acetylcholine Release in the Ventral Hippocampus in Rats

Kenichi Mishima1, Katsunori Iwasaki1, Hiroshi Tsukikawa1, Yoshiaki Matsumoto2, Nobuaki Egashira1, Kohji Abe1, Takashi Egawa1 and Michihiro Fujiwara1,*

1Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
2Department of Pharmacology, School Nurse Training, Kyushu Women's Jr. College, Kitakyushu 807-8586, Japan
*Corresponding author.  FAX:+81-92-863-0389

Abstract: We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 mg, i.c.v.) and pirenzepine (80 mg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 mg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 mg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.

Keywords: Spatial cognition, 8-Arm radial maze task, Acetylcholine release, Scopolamine,
Ventral hippocampus

Copyright© The Japanese Pharmacological Society 2000

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