Inhibition of THIP on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.
This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor super-sensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
Yoon
In-Seup
IS
Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Shin
Im-Chul
IC
Hong
Jin-Tae
JT
Lee
Myung-Koo
MK
Oh
Ki-Wan
KW
D000818:Animals; D004361:Drug Tolerance; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors*; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles; D011954:Receptors, Dopamine; D009020:Morphine; C015542:gaboxadol