title: Inhibition of THIP on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.
abstract: 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.
authors: Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, Korea.
authors: In-Seup
authors: IS
authors: Yoon
authors: Im-Chul
authors: IC
authors: Shin
authors: Jin-Tae
authors: JT
authors: Hong
authors: Myung-Koo
authors: MK
authors: Lee
authors: Ki-Wan
authors: KW
authors: Oh
mesh_terms: 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*
chemical_list: D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles; D011954:Receptors, Dopamine; D009020:Morphine; C015542:gaboxadol