ALPHA(1)-ADRENOCEPTOR ANTAGONISTS DIFFERENTIALLY CONTROL SEROTONIN RELEASE IN THE HIPPOCAMPUS AND STRIATUM - A MICRODIALYSIS STUDY

Using the in vivo microdialysis technique, we have studied the effect of the systemic administration of several alpha(1)-adrenoceptor antagonists on the extracellular levels of serotonin (5-HT) in the rat hippocampus. Prazosin, and to a lesser extent, terazosin, decreased these levels by 50-60% for 0.03-0.4 mg/kg, i.v. and by 30-40% for 0.1-0.4 mg/kg, i.v., respectively. In contrast, alfuzosin, an alpha(1)-adrenoceptor antagonist with poor brain penetration, did not significantly affect these levels even at the high dose of 0.4 mg/kg, i.v. When perfused into the hippocampus through the dialysis probe, prazosin (1-10 mu M) induced a more limited (20-30%) and delayed decrease in 5-HT outflow. These results support the existence of central noradrenergic facilitatory influence, mediated by alpha(1)-adrenoceptors, on serotonergic neurons projecting to the hippocampus. In the striatum prazosin (0.4 mg/kg, i.v.) decreased 5-HT levels to a smaller extent (-35%) than in the hippocampus (-65%), suggesting the existence of differences in the degree of noradrenergic influence on median and dorsal raphe nuclei, which preferentially project to the hippocampus and striatum, respectively.