The possible cross-tolerance between morphine- and nicotine-induced hypothermia in mice

In the present study, cross-tolerance between hypothermia induced by morphi ne and nicotine in mice has been investigated. Different doses of morphine or nicotine induced dose-dependent hypothermia. The sub-maximal doses of bo th drugs were used for interaction studies. Administration of mecamylamine either intracerebroventricularly (2-6 mug/animal icv) or intraperitoneally (0.5 and 1 mg/kg ip) decreased both morphine- or nicotine-induced hypotherm ia. Naloxone either intracerebroventricularly (2-6 mug/animal) or intraperi toneally (1 and 2 mg/kg) reduced the response to morphine, but not nicotine 's response. Hexamethonium (5 and 10 mg/kg ip) caused a slight decrease in morphine's hypothermia, but not that of nicotine. Nicotine's response was d ecreased in the animals which were made tolerant to hypothermic effect of m orphine, pre-treatment of the animals with low doses of morphine (12.5 or 2 5 mg/kg), once daily for 3 days, did not cause significant tolerance to the hypothermic response to morphine or nicotine. However, the administration of low doses of morphine (12.5 or 25 mg/kg) plus nicotine (2 mg/kg), once d aily for 3 days, increased levels of tolerance to hypothermia induced by ei ther drug. It is concluded that nicotinic receptor mechanism may play a rol e in morphine-induced hypothermia and there is cross-tolerance between the two drugs. (C) 2001 Elsevier Science Inc. All rights reserved.