The development of cross-tolerance between morphine and nicotine in mice.

In the present study, cross-tolerance between nicotine and morphine in mice has been investigated. Mice were treated subcutaneously with three doses of morphine (12.5, 25 and 50 mg/kg) once daily, for 3 days in order to produce tolerance to morphine and nicotine antinociception. Tolerance only developed in the high dose group. On the 4th day, the antinociceptive effect of three test doses of morphine (3, 6 and 9 mg/kg) or nicotine (0.01, 0.05 and 0.1 mg/kg) were assessed. Tolerance to the responses of both drugs were observed. Intraperitoneal administration of nicotine (2 mg/kg) three times a day for a period of 12 days, also induced tolerance to the antinociceptive effects of both morphine and nicotine. When animals were tested on the 13th day, the antinociceptive responses of morphine or nicotine were reduced. Another group of animals was treated with low doses of morphine daily (12.5 or 25 mg/kg) plus nicotine (2 mg/kg) three times daily for 3 days. In this group of animals, the antinociception to either morphine or nicotine was tested. Combination of both drugs caused an increase in tolerance to either drug. It is concluded that there is cross-tolerance between the two drugs.