Differential effects of three acute stressors on the serotonin 5-HT1A receptor system in rat brain.

The effects of different acute stressors on circulating corticosterone levels, 5-HT1A receptors and 5-HT1A mRNA levels were measured in male Sprague-Dawley rats. Two hours restraint stress, short swim stress (15 min) and long swim stress (30 min) increased circulating corticosterone levels 10-, 13- and 18-fold, respectively, when measured immediately after termination of the stress. Each stressor produced a unique profile of changes in 5-HT1A receptors measured in coronal sections 24 h after the termination of stress with the antagonist [125I]-4-(2'-methoxyphenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido ] ethylpiperazine and the agonist [3H]-8-hydroxy-2-(di-n-propylamino)tetralin. Restraint stress produced decreases in antagonist binding in the CA3 region and dentate gyrus: agonist binding was decreased only in the dentate gyrus. Despite the larger elevation in circulating corticosterone level measured after short swim stress, no changes in agonist or antagonist binding were detected after this stressor. In contrast, the long swim stress increased antagonist binding in the CA2 region and in layers IV-VI of the cortex: agonist binding was also increased in all regions of the hippocampus and in layers I-VI of the cortex. Thus, restraint and long swim stress produce opposite effects on 5-HT1A receptor expression in different subregions of the hippocampus. Analysis of presynaptic 5-HT1A receptors in the raphe nuclei revealed an increase in antagonist binding in the dorsal raphe following long swim stress. No change in the level of 5-HT1A mRNA measured in adjacent sections was detected following any of the stressors. The role of corticosteroid receptors in these stress-induced alterations of 5-HT1A receptors and the potential significance of these alterations in the context of affective disorders are discussed.