DIFFERENTIAL-EFFECTS OF 5,7-DIHYDROXYTRYPTAMINE-INDUCED SEROTONINERGIC DEGENERATION ON 5-HT1A RECEPTORS AND 5-HT UPTAKE SITES IN THE RAT-BRAIN

The time-course of 5,7-dihydroxytryptamine-induced lesions (2, 5 and 1 4 days after i.c.v. injection of 150 mu g) and the effects of acute re serpine treatment (10 mg/kg, i.p., one or 5 days before scheduled deat h), were evaluated by autoradiography of [H-3]paroxetine binding sites in the rat brain. Reserpine had no significant effect on [H-3]paroxet ine binding, indicating that the depletion of serotonin is not suffici ent per se to alter the serotonin uptake sites in any region. Two days after the 5,7-dihydroxytryptamine lesion, [H-3]paroxetine binding was already decreased in the majority of brain regions. In the caudate pu tamen these binding sites were significantly decreased only 14 days af ter the lesion, whereas the ventral tegmental area (or the enclosed me dian forebrain bundle), the dorsal raphe (mainly the ventral portion) and the median raphe maintained their high density of serotonin uptake sites even after 14 days. Results were similar using [H-3]citalopram as ligand for the serotonin uptake sites, in the brains of rats lesion ed 5 days before death; an exception was the ventral portion of the do rsal raphe, where there was a significant increase with [H-3]paroxetin e and a decrease with [H-3]citalopram binding. In adjacent sections of the same brains we also measured [H-3]8-OH-DPAT binding, confirming t hat it completely disappears in the dorsal raphe after the lesion. Thu s, considering the extent of serotonin cell body degeneration, there a ppears to be a paradoxical;mismatch between the excessive loss of [H-3 ]8-OH-DPAT binding and the resistance of [H-3]citalopram or [H-3]parox etine binding in the dorsal raphe, suggesting that the two binding sit es may undergo adaptive regulation in surviving neurons.