Modification of the antinociceptive effect of morphine by acute and chronic administration of clomipramine in mice.

The antinociception effect of clomipramine and the combination of clomipramine and morphine was evaluated using the constant temperature hot plate test, the increasing temperature hot plate test and the formalin test in mice. Both a single dose of clomipramine (10 mg/kg) given intraperitoneally (i.p.) and chronic clomipramine treatment (10 mg/kg/day, i.p., for 7 days) induced antinociception. When morphine (5 mg/kg), given subcutaneously (s.c.), and clomipramine were combined, an increased antinociceptive effect compared to morphine alone was observed in all tests. In the increased temperature hot plate test and in the formalin test increased antinociception was also observed when morphine was combined with chronic clomipramine treatment. In the constant temperature hot plate test no additional effect compared to morphine alone was observed when morphine and chronic clomipramine treatment were combined. These results indicate that clomipramine has an antinociceptive effect in itself, and that it may enhance the antinociceptive effects of morphine. The differences between the tests indicate that different nociceptive mechanisms are involved, and that the combination of clomipramine and morphine may be beneficial for some types of nociceptive stimuli, but not for others.