Antidepressant drugs potentiate the alpha 1-adrenoceptor effect in hippocampal slices

The effect of prolonged treatment with antidepressant drugs on the phenylephrine- and norepinephrine (NE)-evoked reaction in hippocampal slices was examined by extracellular recording of the spontaneous activity of CA1 layer neurons. The alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, depressed the neuronal discharges of most of the units tested, while NE evoked both excitatory and inhibitory effects which were blocked by propranolol and phentolamine or prazosin, respectively. Imipramine, mianserin, (+)- and (-)-oxaprotiline administered subchronically (10 mg/kg p.o., twice daily for 14 days, withdrawal 48 h), potentiated the inhibitory reaction to phenylephrine. Mianserin was the only drug tested in the acute dose to effectively augment the reaction to alpha 1-adrenoceptor stimulation. Prolonged administration of mianserin and imipramine attenuated the excitatory effect to NE, which probably reflects beta-receptor down-regulation; however, only mianserin, but not imipramine, enhanced the NE-induced inhibition. The observed potentiation of the alpha 1-adrenoceptor-related inhibitory reaction to phenylephrine produced by antidepressant drugs may reflect the development of the alpha 1-adrenergic system supersensitivity in the hippocampus.