Dynamics of Central Nervous 5-HT1A-Receptors under Psychosocial Stress

Abstract

It is well established that stress leads to changes in the serotonergic system. In order to gain a better understanding of the effects of recurrent stressful experiences on the serotonergic system, changes in the 5-HT1A-receptor system resulting from different periods of psychosocial stress (PSS) were analyzed in the present study. Male tree shrews (Tupaia belangeri) were submitted to subordination stress for 2, 10, 21, and 28 d. 5-HT1A-receptor binding was quantified by in vitro receptor autoradiography using the agonist 3H-8-OH-DPAT (3H-8-hydroxy-2-(di-n-propylamino)tetralin. PSS caused a downregulation of 3H-8-OH-DPAT binding sites in cortical areas and in the hippocampus. After 10, 21, and 28 d of PSS, the number of binding sites was reduced in layers V and VI of the posterior cingulate cortex (by 34%). After 28 d of PSS, the number of binding sites was reduced in the parietal cortex (by 18%), in the prefrontal cortex (by 16%), in the regio retrobulbaris (by 8%), and in region CA1 of the hippocampus (by 11%). In the raphe nuclei, no PSS-induced downregulation of 5-HT1A-receptors occured. A transient increase in 3H-8-OH-DPAT binding was observed in the claustrum after 2 d of PSS (by 15%). There were also transient decreases in affinities for the radioligand probably representing receptor desensitization, for example, in the dorsal raphe nucleus after 28 d of PSS. In conclusion, the dynamic 5-HT1A-receptor changes occuring during PSS include downregulation and transient desensitization of receptors. They reflect regulatory mechanisms which probably lead to destabilization of the serotonergic system during prolonged PSS.