Effect of methamphetamine and imipramine on cerebral ischemia-induced hyperactivity in Mongolian gerbils.

Abstract

Ischemia-induced hyperactivity is recognized several hours after both common carotid arteries' occlusion for 5 min in Mongolian gerbils, and it continues for at least 7 days. The aim of this study is to investigate the possible mechanisms of this abnormal behavior. Methamphetamine (MAP) (1 and 3 mg /kg) was administered for 7 days and imipramine (IMP) (5 and 10 mg/kg) was administered for 7 or 14 days. Bilateral carotid artery was occluded for 5 min 24 h after the last administrations of these drugs. MAP, which had been administered every day for 1 week, showed marked inhibition in the ischemia-induced hyperactivity. However, IMP did not have any effect even though it had been injected every day for 2 weeks. Hippocampal CA1 neuronal changes also appeared in the MAP- and IMP-administered groups. As the dopaminergic neurotransmission is facilitated by the repeated administration of MAP, the ischemia-induced hyperactivity may be related to abnormalities in dopaminergic function. The participation of the other neurotransmitters is also discussed.