Differential changes in glutamatergic transmission via N-methyl-D-aspartate receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine.
We searched for changes in glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine (Meth). Prior to being given a challenge dose of Meth (2 mg/kg, s.c.), the rats were given Meth (4 mg/kg, s.c.) five times a week for 3 wk. Seven days after the challenge test, we examined glutamate (Glu) release from hippocampal and striatal slices evoked by 30 mm KCl, and NMDA-evoked dopamine (DA) release from striatal slices. We further immunoquantified NMDAR1, R2A and R2B receptors as well as the fodrin alpha-subunit, a 240 kDa cytoskeletal protein that is cleaved to form 150 kDa limited proteolytic fragments by NMDA receptor stimulation. In the study of KCl-evoked Glu release, Glu release from the hippocampus was 31% lower in the Meth-sensitized rats than in the control rats, while Glu release from the striatum was 34% higher in the Meth-sensitized rats. NMDAR1, R2A and R2B immunoreactivities in the striatum were significantly lower in the Meth-sensitized rats (by 12, 13 and 12%, respectively) than those in the control rats. However, no differences in the immunoreactivities were found for the hippocampus. Immunoquantification of the fodrin alpha-subunit in the hippocampus revealed that 150 kDa fragments were significantly lower (by 10%) in the Meth-sensitized rats than in the control rats. In contrast to the control rats, NMDA-evoked DA release from the striatum was diminished in the Meth-sensitized rats. These results indicate that the activity of the Glu system is functionally decreased in the hippocampus of Meth-sensitized rats, whereas the Glu system in the striatum of Meth- sensitized rats shows adaptive and functional changes in the receptors in response to the increased Glu release.
Yamamoto
Hideo
H
Department of Psychiatry and Neurology, Kobe University School of Medicine, Kobe 650-0017, Japan.
Kitamura
Noboru
N
Lin
Xian-Hao
XH
Ikeuchi
Youji
Y
Hashimoto
Takeshi
T
Shirakawa
Osamu
O
Maeda
Kiyoshi
K