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) neurotransmission by attenuating the release of endogenous norepinephrine (NE), as a result of the activation of alpha-2 adrenergic autoreceptors on NE neurons, and that high doses decrease 5-HT neurotransmission by activating directly alpha-2 adrenergic heteroreceptors on 5-HT terminals. In addition, we have shown that long-term treatments with a monoamine oxidase inhibitor or a selective NE, but not a 5-HT, reuptake inhibitor 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 determine 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 electroconvulsive shocks (6 or 7 over a 2-week period) would also affect the alpha-2 adrenoceptors modulating 5-HT neurotransmission in the rat hippocampus. The responsiveness of these hetereceptors was tested in parallel with those of the terminal 5-HT1B autoreceptors and of the postsynaptic 5-HT1A and alpha-2 adrenergic receptors. None of the above treatments altered the responsiveness of the 5-HT1B autoreceptors, as assessed by comparing the differential effectiveness of 1 and 5 Hz electrical stimulations of the 5-HT pathway. Idazoxan and mianserin did not affect the responsiveness of the postsynaptic 5-HT1A and alpha-2 adrenergic receptors as indicated by the unchanged suppressant effects of microiontophoretically applied 5-HT and NE.(ABSTRACT TRUNCATED AT 250 WORDS)
Mongeau
R
R
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
de Montigny
C
C
Blier
P
P
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004565:Electroconvulsive Therapy; D019329:Idazoxan; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D008803:Mianserin; D012701:Serotonin; D003000:Clonidine; D019329:Idazoxan