Inhibition of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.
This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity as measured in mice, and the morphine-induced hyperactivity was inhibited dose-dependently by the administration of the GABA(A) agonist, muscimol (0.3, 0.5 and 1.0 mg kg(-1) i.p.). However, daily repeated administration of morphine caused the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.). The administration of muscimol inhibited the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.) in mice that had received chronic administration of morphine. Postsynaptic dopamine receptor supersensitivity, as shown by the enhanced ambulatory activity after administration of apomorphine (2 mg kg(-1) s.c.), also developed in reverse-tolerant mice. Muscimol also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited via the activation of GABA(A) receptors.
Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
In-Seup
IS
Yoon
Hack-Seang
HS
Kim
Jin-Tae
JT
Hong
Myuhg-Koo
MK
Lee
Ki-Wan
KW
Oh
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004361:Drug Tolerance; D018755:GABA Agonists / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000523:psychology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
D018755:GABA Agonists; D009294:Narcotics; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D009118:Muscimol; D009020:Morphine