Role of GABAergic Systems in the Development of Morphine Tolerance in Formalin-Treated Mice
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概要
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Since the development of tolerance to morphine antinociception in formalin-treated mice was delayed and diazepam normalized the delay, the involvement of GABAergic systems in the process was investigated. Gamma amino-a<I>n</I>-butyric acid (GABA) at 10 mg/kg and the GABA<SUB>A</SUB>-receptor agonist muscimol at 0.05 mg/kg, i.p., 30 min before daily morphine injection at 10 mg/kg, s.c. completely reversed the delay in the development of morphine tolerance in the formalin-treated mice. The GABA<SUB>A</SUB> antagonist bicuculline at 1 mg/kg and the Cl<SUP>-</SUP>-channel blocker picrotoxin at 1 mg/kg extinguished the reverse effect of muscimol and GABA, respectively. In contrast, the GABA<SUB>B</SUB> antagonist CGP 35348 (3-aminopropane-diethoxymethyl-phosphinic acid) up to 100 mg/kg, i.p. failed to abolish the GABA effect; and baclofen, a GABA<SUB>B</SUB>-receptor agonist, at 0.5 and 2 mg/kg, i.p., 30 min before morphine was without effect on the delay. On the other hand, bicuculline was incapable of abolishing the reverse effects of diazepam on the delay of tolerance development; and likewise, the reverse effect of muscimol was not affected by flumazenil. No appreciable influence of these GABA-related compounds was seen on morphine antinociception itself nor the development of tolerance in normal mice. These results suggest that the benzodiazepine-GABA<SUB>A</SUB>-Cl<SUP>-</SUP> channel complex is involved in the mechanism underlying the delay of the development of morphine tolerance in formalin-treated mice; however, it is deduced that benzodiazepine-receptor and GABAergic systems are not always functionally coupled to each other in the mechanisms.
- 社団法人 日本薬理学会の論文
- 1995-06-01
著者
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Takahashi Masakatsu
Department Of Pharmacoinformatics School Of Pharmaceutical Sciences Nagasaki University
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Kaneto H
Nagasaki Univ. Nagasaki Jpn
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Kaneto Hiroshi
Department Of Pharmacology Faculty Of Pharmaceutical Science Nagasaki University
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Takahashi Masakatsu
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Nagasaki University
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RAHMAN A.F.M.Mohibur
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University
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Rahman A.f.m.mohibur
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Nagasaki University
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