Inhibition of THIP on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity
| Autor: | In-Seup Yoon, Im-Chul Shin, Ki-Wan Oh, Jin-Tae Hong, Myung Koo Lee |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Male medicine.drug_class Pharmacology Motor Activity Receptors Dopamine Mice Dopamine receptor D1 Dopamine receptor D3 Postsynaptic potential Dopamine receptor D2 Drug Discovery medicine Animals GABA-A Receptor Agonists GABA Agonists Mice Inbred ICR Morphine Chemistry Organic Chemistry Drug Tolerance Isoxazoles Apomorphine Dopamine receptor Molecular Medicine Reverse tolerance medicine.drug |
| Zdroj: | Archives of pharmacal research. 25(2) |
| ISSN: | 0253-6269 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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