The binding of a highly specific ligand for serotonin (5-HT) uptake sites, [3H]paroxetine, was studied in brain regions of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR). [3H]Paroxetine bound to a single, high affinity binding site in the brain. In midbrain, the density (Bmax values) of [3H]paroxetine binding were significantly reduced (27.16%) in SHR as compared to WKY. The affinity (Kd values) were found to be similar in SHR and WKY. The Kd and Bmax values of [3H]paroxetine binding were found to be similar in spinal cord, pons and medulla and cerebral cortex of WKY and SHR. The effect of centrally acting hypotensive agents, clonidine and centhaquin, on [3H]paroxetine binding was also determined and compared with imipramine, a known 5-HT uptake inhibitor. Clonidine did not displace [3H]paroxetine binding at any concentration (10(-4) to 10(-7) M). On the other hand, centhaquin, which produces hypotension similar to clonidine, could displace [3H]paroxetine binding in a concentration dependent manner. In cerebral cortex and brainstem (midbrain, pons and medulla) membranes, the IC50 values of imipramine and centhaquin for [3H]paroxetine binding were found to be similar in WKY and SHR. The IC50 of centhaquin in displacing paroxetine from 5-HT uptake sites, was 10 times lower in the cerebral cortex and 4 times lower in the brainstem membranes when compared to imipramine. Clonidine had no effect on 5-HT uptake sites. The results indicate that (1) the density of 5-HT uptake sites is reduced in the midbrain of hypertensive rats, and (2) centhaquin, a centrally acting hypotensive agent, acts on 5-HT transporter sites.(ABSTRACT TRUNCATED AT 250 WORDS)