Effects of imipramine on central serotonergic and noradrenegic interaction in mice

Fenfluamine, a serotonin (5-HT) releaser, 5-hydroxytryptophan (5-HTP), a 5-HT precursor, and 5-methoxy -N, N-dimethltryptamine (5-MeODMT), a 5-Ht receptor agonist, induced head twitch responses in mice. A single injection of imipramine as well as clonidine (α_2 receptor agonist) inhibited head twihches induced by these drugs. Yohimbine (α_2 receptor antagonist) antagonized inhibitory effects of imipramine and clonidine on the behaviors. Repeated treatment with imipramine as well as single dose of yohimbine potentiated the behaviors induced by these serotonin afonists. α-Methyl-p-tyosine (αMPT : tyrosine hydrozylase inhibitor) inhibited head twitched induced by fenfluramine and 5-HTP but did not affect those by 5-MeODMT. P-Chlorophenylalanine (PCPA : tryptophan hydroxylase inhibitor) inhibited head twitches induced by fenfluramine, while it did not affect those by 5-HTP and potentiated those by 5-MeODMT. PCPA antafonized the inhibitory effect of α-MPT on head twitchedinduced by 5-HTP but did not antafonized the inhibitory effects of imipramine nad clonidine. Through α-MTP did not affect head twitches induced by 5-MeODMT, the drug antagonized those potentiated bu PCPA. Imipramine and clonidine also inhibited head twitches induced by-5-MeODMT potentinergic neurons is similar to a mode of action of clonidine, and chronic effect of the drug is qute alike actue effect of yohimbine. Fenfluramine and 5-HTP which act via presynapse od serotonergic neurous require endogenous catecholamine, especially noradrenalline, for the wxpression of head twitches. But 5-MeODMT witch directly abt on postsynaptic receptors dose not rewuire them. Furthermore, rate-limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase may act conpetitively each other in presynaptic sites and maintain the balance between noradrenaline and 5-HT in presynapses.