Zarrindast M R, Barghi-Lashkari S, Shafizadeh M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Pharmacol Biochem Behav. 2001 Feb;68(2):283-9. doi: 10.1016/s0091-3057(00)00457-3.
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.
在本研究中，已对吗啡和尼古丁诱导的小鼠体温过低之间的交叉耐受性进行了研究。不同剂量的吗啡或尼古丁可诱导剂量依赖性体温过低。两种药物的次最大剂量用于相互作用研究。脑室内注射美加明（2 - 6微克/动物，脑室内注射）或腹腔注射（0.5和1毫克/千克，腹腔注射）均可降低吗啡或尼古丁诱导的体温过低。脑室内注射（2 - 6微克/动物）或腹腔注射（分别为1和2毫克/千克）纳洛酮可降低对吗啡的反应，但不影响对尼古丁的反应。六甲铵（5和10毫克/千克，腹腔注射）可使吗啡诱导的体温过低略有降低，但对尼古丁诱导的体温过低无影响。在对吗啡体温过低效应产生耐受性的动物中，尼古丁的反应降低。对动物每日一次连续3天给予低剂量吗啡（12.5或25毫克/千克）预处理，不会导致对吗啡或尼古丁体温过低反应产生显著耐受性。然而，每日一次连续3天给予低剂量吗啡（12.这两种药物之间存在交叉耐受性。
