Effect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors.

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 micrograms/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the Bmax values for 3H-ketanserin binding without any change in the Kd values. Moreover, this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (+/-)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (+/-)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropin-adrenal axis activation of rats increases both the number of 5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced by (+/-)DOI.