Effects of 5-HT1A Receptor Agonists on Hypothalamo-pituitary-adrenal Axis Activity and Corticotropin-releasing Factor Containing Neurons in the Rat Brain

Corticotropin-releasing factor (CRF) is the major physiological regulator of the hypothalamo-pituitary-adrenal axis. There is evidence that CRF release from the hypothalamus is under stimulatory serotonergic control. The specific 5-HT receptor subtypes that mediate this effect is unclear. Administration of the 5-HT1A agonists, 8-OH-DPAT (1 mg/kg) and ipsapirone (4 mg/kg), to rats resulted in activation of the HPA axis as evidenced by increased plasma ACTH and corticosterone concentrations in acutely treated rats and increased plasma corticosterone concentrations in both acutely and chronically treated rats. However, chronic administration of these compounds failed to alter CRF concentrations in the medium eminence or CRF receptor number of affinity in the anterior pituitary. Chronic administration of both compounds resulted in increased CRF concentrations in the piriform cortex and hippocampus, whereas 8-OH-DPAT alone increased CRF concentrations in the amygdala and entorhinal cortex. These results suggest that both hypothalamic and extrahypothalamic CRF neurons are influenced by activation of 5-HT1A receptors.