Electrophysiological and receptor studies in rat brain: effects of clorgyline.

Acute high doses of clorgyline produce a rapid inhibition of monoamine oxidase type A (MAO A) in the rat brain, together with an increase in norepinephrine and a decrease in the firing rate of locus coeruleus (LC) neurones: this decrease is reversed by piperoxane, an alpha 2 antagonist. In control animals, piperoxane increases LC neuronal firing showing that these noradrenergic neurones are under alpha 2-adrenoceptor-mediated tonic inhibition. Chronic administration of clorgyline, like acute doses of this MAO A inhibitor, significantly decreases cell firing in the LC and the effect is partially reversed by piperoxane. Chronic clorgyline treatment also produces significant decreases in [3H]clonidine and [3H]dihydroalprenolol binding in cerebral cortex, receptor changes which are slightly greater in animals showing greater inhibition of LC neuronal firing: such receptor changes do not occur following a single exposure to clorgyline. Electrophysiological studies in hippocampal pyramidal cells show that the chronic clorgyline treatment does not significantly induced subsensitivity to NE in these adrenoreceptive cells.