CHRONIC IMIPRAMINE TREATMENT INDUCES DOWN-REGULATION OF ALPHA-2 RECEPTORS IN RATS LOCUS-COERULEUS AND A2 REGION OF THE TRACTUS-SOLITARIUS

Imipramine is an effective antidrepressant agent that blocks the reupt ake of monoamines. In order to understand some of its basic mechanisms of action, we investigated the effects of chronic imipramine administ ration (10mg/kg, i.p.; 21 days) on the alpha-2 receptor population of several brain sites. Alpha-2 receptor density was estimated by in vitr o autoradiography using [H-3]daxozan. The densitometric analysis revea led a decreased receptor density in the A2 region of the tractus solit arius (20%) and locus coeruleus (16%). No changes were observed in the amygdala, pyriform cortex, periacueductal gray and the bed nucleus of the stria terminalis. These results suggest that chronic imipramine t reatment selectively modulates the alpha-2 receptor population localiz ed in the brain stem norepinephrine-rich nuclei and not in the populat ion present on limbic structures innervated by noradrenergic terminal projections. The possible physiological consequences of this selective modulation of alpha-2 receptors are discussed.