6-Hydroxydopamine pretreatment effects on alpha- and beta-adrenergic receptor adaptation to clorgyline

Abstract

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.