بررسی اثر و مکانیسم های اوپیوییدی و دوپامینرژیک دکسترومتورفان بر پاسخ درد ایجاد شده با اسید استیک در موش ها با استفاده از تست Writhing شکمی

Background and purpose: Dextromenthorphan is a NMDÂ receptor antagonist in the glutamatergic system. Çurrently, there are good reports showing that the glutamatergic NMDÂ receptor mechanism modulates endogenous opiods and dopamine actions in several brain regions. This effect may in part change pain threshold in various analgesic tests. The purpose of the present study is to determine the modulatory effect of dextromethorphan on the pain threshold in the mouse writhing test. Materials and methods: Ïntraperitoneal (i.p.) injection of acetic acid (10 ml/kg, 0.6%) produces abdominal writhing in mice. The number of writhes occurring during a 30 min period after acetic acid injection was recorded. Results: Dextromenthorphan (30 mg/kg, i.p.) caused a significant reduction in acetic acid-induced writhing behavior. The dose of 30 mg/kg, i.p., of dextromethorphan also potentiated mortphine (1-8 mg/kg, s.c.) antinociception. The antinociceptive effect of dextromethorphan was blocked by either naloxone (0.5 mg/kg, i.p.) or apomorphine (0.25-2 mg/kg, s.c.). The effect of apomorphine was antagonized by the dopamine D1 receptor antagonist, SÇH 23390 (1mg/kg, i.p.) but not by the dopamine D2 receptor antagonist, sulpiride (50 mg/kg, s.c.) nor the peripheral dopamine receptor antagonist, domperidone (10 mg/kg, s.c.). Çonclusion: These results suggest that the opioid and central dopamine D1 receptor mechanisms may in part mediate the antinociceptive effect of dextromethorphan in the mouse writhing test.