6-Hydroxydopamine pretreatment effects on alpha- and beta-adrenergic receptor adaptation to clorgyline.
The effects of 6-hydroxydopamine (6-OHDA) lesions on brain adrenergic receptor adaptation to 21 days of treatment with the selective monoamine oxidase type A (MAO-A) inhibitor clorgyline were studied in rats. 6-OHDA pretreatment effectively blocked the decrease in alpha 1-, alpha 2- and beta-adrenergic receptor densities observed in response to clorgyline treatment. In saline-treated rats, 6-OHDA reduced norepinephrine (NE) to 8% of control levels, modestly reduced dopamine (DA) to 67% of controls, but did not affect serotonin (5HT) levels in the cortex, Clorgyline administration to shams increased NE and 5HT to 239% and 160% of their respective control levels, but did not effect DA levels. 6-OHDA lesions attenuated clorgyline's effect on cortical NE levels but not 5HT. The results suggest that beta-adrenergic receptor adaptation to MAOI's as with tricyclic antidepressants is a response to an increase in catecholamine receptor occupancy, and that a similar molecular mechanism is responsible for the observed clorgyline induced changes in alpha-adrenergic receptors.
Cohen
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RM
Aulakh
C
C
McLellan
C
C
Murphy
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DL
D000818:Animals; D001921:Brain / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D006892:Hydroxydopamines; D011437:Propylamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D016627:Oxidopamine; D003010:Clorgyline; D004298:Dopamine; D009638:Norepinephrine