The possible cross-tolerance between morphine- and nicotine-induced hypothermia in mice.
In the present study, cross-tolerance between hypothermia induced by morphine and nicotine in mice has been investigated. Different doses of morphine or nicotine induced dose-dependent hypothermia. The sub-maximal doses of both drugs were used for interaction studies. Administration of mecamylamine either intracerebroventricularly (2-6 microg/animal icv) or intraperitoneally (0.5 and 1 mg/kg ip) decreased both morphine- or nicotine-induced hypothermia. Naloxone either intracerebroventricularly (2-6 microg/animal) or intraperitoneally (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 decreased in the animals which were made tolerant to hypothermic effect of morphine. Pre-treatment of the animals with low doses of morphine (12.5 or 25 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 daily for 3 days, increased levels of tolerance to hypothermia induced by either drug. It is concluded that nicotinic receptor mechanism may play a role in morphine-induced hypothermia and there is cross-tolerance between the two drugs.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. zarinmr@ams.ac.ir
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Zarrindast
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Barghi-Lashkari
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Shafizadeh
D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D007036:Hypothermia, Induced / Q000379:methods; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology
D009292:Narcotic Antagonists; D009294:Narcotics; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009270:Naloxone; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine