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.
Campbell
I C
IC
Gallager
D W
DW
Hamburg
M A
MA
Tallman
J F
JF
Murphy
D L
DL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D011437:Propylamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008995:Monoamine Oxidase; D003010:Clorgyline; D009638:Norepinephrine