Effects of imipramine on the expression and development of morphine dependence in mice

In the present study, the effects of imipramine and/or alpha-adrenoceptor agents on naloxone-induced jumping in morphine-dependent mice were examined. In the first set of experiments, the drugs were used before naloxone injection, to test their effects on the expression of jumping. Administration of imipramine (10-60 mg/kg) 15 min before naloxone increased the number of jumping in mice. Injection of the alpha2-adrenoceptor agonist, clonidine (0.1 mg/kg), or alpha1-adrenoceptor agonist, phenylephrine (4 mg/kg), themselves neither altered naloxone-induced jumping nor influenced the imipramine response. The alpha2-adrenoceptor antagonist, yohimbine (4 mg/kg), itself but not the alpha1-adrenoceptor antagonist, prazosin (1 mg/kg), increased jumping and decreased the imipramine effect. In the second set of experiments, imipramine and/or the alpha-adrenoceptor drugs were injected during the development of morphine dependence. Imipramine (10-40 mg/kg) increased the development of dependence and increased jumping was seen. Clonidine did not influence the imipramine effect. Phenylephrine was lethal in combination with imipramine. Both yohimbine and prazosin decreased the effect of imipramine. Imipramine and phenylephrine but not clonidine, yohimbine or prazosin decreased locomotion. It is concluded an alpha2-adrenoceptor mechanism may be involved in the influence of imipramine on the expression and development of naloxone-induced withdrawal signs in mice.