Quantitative autoradiography of 5-hydroxytryptamine1A binding sites in rats with chronic neonatal...

We recently reported that rats with elevated brainstem serotonin (5-HT) concentration and 5-HT transporter binding site density after neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions made by intraperitoneal (i.p.) injection exhibited more myoclonic supersensitivity to the 5-HT1A agonist 8-OH-DPAT than those with decreased brainstem 5-HT and 5-HT transporter sites following intracisternal 5,7-DHT (i.c.) injection. To investigate the role of 5-HT1A receptors in these differences, we labelled 5-HT1A binding sites autoradiographically with [3H]8-OH-DPAT 4 months after i.p. or i.c. 5,7-DHT or saline in the first week postnatal. The regional distribution of 5-HT1A sites conformed to previous reports of highest receptor densities in hippocampus (CA1, dentate gyrus), septal nuclei, dorsal and median raphe, mammillary body, and certain cortical regions (cingulum, claustrum). 5-HT1A binding was significantly decreased (-87%) in the dorsal raphe after i.c.-made 5,7-DHT lesions. No reductions were found after lesions made by i.p. injection compared to controls, but rather a 246% increase in area of 5-HT1A binding extending from the dorsal raphe was observed. These changes in 5-HT1A binding sites in the dorsal raphe in the chronic phase of 5,7-DHT lesions may contribute to the different behavioral consequences of the route of neonatal 5,7-DHT injection.