| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The role of the N-methyl-D-aspartate (NMDA) receptors in hyperlocomotion induced by MK-801, a potent and selective non-competitive NMDA receptor antagonist, was examined in mice. A low dose of MK-801 [0.2 mg/kg, intraperitoneally (IP) ] produced a marked increase in locomotor activity without obvious staggering gait. NMDA (60-120 mg/kg, IP) , an NMDA receptor agonist, partially but significantly antagonized hyperlocomotion induced by MK-801 (0.2 mg/kg). On the other hand, neither a high dose of N-methyl-L-aspartate (400 mg/kg, IP) , a stereoisomer of NMDA,nor a critical subconvulsive dose of kainate (10 mg/kg, IP) , a non-NMDA receptor agonist, reversed MK-801-induced hyperlocomotion. The activity induced by MK-801 was potently suppressed by low doses of haloperidol (0.05-0.1 mg/kg, IP) , a dopamine (DA) receptor antagonist, in a dose-dependent manner. These data for MK-801 were similar to those for phencyclidine and ketamine, other non-competitive NMDA receptor antagonists. These results suggest that non-competitive NMDA receptor antagonist-induced hyperlocomotion is mediated, at least in part, by NMDA receptor antagonism, although this hyperactivity may also involve DAergic mechanisms through indirect (perhaps by reducing NMDA receptor-mediated neurotransmission) and/or direct (by increasing DA release or inhibiting DA uptake) effects on DA neurons.
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