EFFECTS OF LONG-TERM ALPHA-2-ADRENERGIC ANTAGONISTS AND ELECTROCONVULSIVE TREATMENTS ON THE ALPHA-2-ADRENOCEPTORS MODULATING SEROTONIN NEUROTRANSMISSION

Previous results from our laboratory indicate that small doses of the alpha-2 adrenergic agonist clonidine increase serotonin (5-HT) neurotr ansmission by attenuating the release of endogenous norepinephrine (NE ), as a result of the activation of alpha-2 adrenergic autoreceptors o n NE neurons, and that high doses decrease 5-HT neurotransmission by a ctivating directly alpha-2 adrenergic heteroreceptors on 5-HT terminal s. In addition, we have shown that long-term treatments with a monoami ne oxidase inhibitor or a selective NE, but not a 5-HT, reuptake inhib itor abolish the effect of a high dose of clonidine, but not that of a small dose of clonidine. The aim of the present study was to determin e whether the alpha-2 adrenergic antagonists idazoxan (10 mg/kg/day x 21 days s.c.) and mianserin (5 mg/kg/day x 21 days s.c.), or electroco nvulsive shocks (6 or 7 over a 2-week period) would also affect the al pha-2 adrenoceptors modulating 5-HT neurotransmission in the rat hippo campus. The responsiveness of these hetereceptors was tested in parall el with those of the terminal 5-HT1B autoreceptors and of the postsyna ptic 5-HT1A and alpha-2 adrenergic receptors. None of the above treatm ents altered the responsiveness of the 5-HT1B autoreceptors, as assess ed by comparing the differential effectiveness of 1 and 5 Hz electrica l stimulations of the 5-HT pathway. Idazoxan and mianserin did not aff ect the responsiveness of the postsynaptic 5-HT1A and alpha-2 adrenerg ic receptors as indicated by the unchanged suppressant effects of micr oiontophoretically applied 5-HT and NE, However, these alpha-2 adrener gic antagonists markedly decreased the reducing effect of 400 mu g/kg i.v. of clonidine on the efficacy of the stimulation of the 5-HT pathw ay, indicating a desensitization of the alpha-2 adrenergic heterorecep tors on 5-HT terminals. Furthermore, the tonic inhibitory action of en dogenous NE on these heteroreceptors was apparently weaker, because th e enhancing effect of 10 mu g/kg i.v. of clonidine also was reduced af ter long-term treatment with these two antagonists. In contrast, these above effects were not induced by repeated electroconvulsive shocks. Consistent with previous findings, the latter treatment increased the efficacy of the stimulation of the 5-HT pathway as well as the suppres sant effect of microiontophoretically applied 5-HT, without altering t hat of NE.