On the mechanism of tolerance to morphine-induced Straub tail reaction in mice

The effect of 5-HT and opioid receptor antagonists on morphine-induced Stra ub tail was studied in mice. Straub tail behavior was induced by subcutaneo us administration of different doses (20, 30, and 40 mg/kg) of morphine hyd rochloride to mice. The effect of morphine was dose-dependent. Maximum resp onse was obtained with 40 mg/kg of the drug. The response induced by morphi ne (20 and 40 mg/kg) was decreased by different doses of intraperitoneal in jection of naloxone (1 and 2 mg/kg) or methysergide, mianserin, and ritanse rin (1 and 2 mg/ kg). The effect of morphine (40 mg/kg) was also reduced by intracerebroventricular injection of naloxone (0.4-0.8 mug/animal) or mian serin (2 and 4 mug/animal). Different groups of mice received one daily dos e (50 mg/kg se) of morphine sulfate for 3 days to develop tolerance to morp hine. The Straub tail reaction induced by morphine hydrochloride (40 mg/kg) was tested on the fourth day. Naloxone injection (1 and 2 mg/kg ip) on Day 3 (1 h after morphine sulfate injection) or on Day 4 (1 h before test dose of morphine hydrochloride), decreased tolerance induced to morphine. Methy sergide, mianserin, or ritanserin (intraperitoneal) on Days 2 and 3 (1 h af ter morphine sulfate injection) or on Day 4 (1 h before test dose of morphi ne hydrochloride), also decreased tolerance induced to morphine. Intracereb roventricular injection of either naloxone or mianserin also reduced tolera nce to morphine. It is concluded that 5-HT2 and opioid receptor mechanisms are involved in morphine-induced Straub tail reaction and tolerance induced to morphine also may be mediated through these receptors. (C) 2001 Elsevie r Science Inc. All rights reserved.