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.ﾊﾊFAX:+81-92-863-0389
E-mail: mfuji@fukuoka-u.ac.jp
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ﾊmg/kg,
i.p. and 20ﾊmg, i.c.v.) and pirenzepine (80ﾊmg,
i.c.v.), but not an M2 antagonist, AF-DX116 (40-80ﾊmg,
i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain
microdialysis with Ringer's solution containing 0.1ﾊmM eserine sulfate,
scopolamine and AF-DX116, but not pirenzepine, increased ACh release in
the VH. Moreover, in the bilateral injection of scopolamine (2ﾊ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ﾊ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ｩ The Japanese Pharmacological Society 2000
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