Journal of Neuroscience, Vol 15, 7132-7140, Copyright © 1995 by Society for Neuroscience
Dynamics of central nervous 5-HT1A-receptors under psychosocial stress
G Flugge
German Primate Center, Gottingen, Germany.
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
occurred. 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 occurring 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.