EFFECTS OF DIVALPROEX SODIUM ON 5-HT1A RECEPTOR FUNCTION IN HEALTHY-HUMAN MALES - HYPOTHERMIC, HORMONAL, AND BEHAVIORAL-RESPONSES TO IPSAPIRONE

Hypothermic and hormonal responses to a challenge with a selective 5-H T1A receptor agonist ipsapirone are considered to provide an index of 5-HT1A receptor function in humans. To examine the effects of divalpro ex sodium (DVP) on 5-HT1A receptor function in humans, we measured the hypothermic, adrenocorticotropic hormone (ACTH) cortisol, and behavio ral responses to ipsapirone in 10 healthy male volunteers. After obtai ning a blood sample for baseline hormone levels and measuring body tem perature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obta ined at regular intervals for three hours. The ipsapirone challenge te sts were repeated after the subjects had been treated with DVP (1000 m g/day) for one week. The results showed that the hypothermia induced b y ipsapirone was significantly attenuated by the DVP treatment, wherea s the ACTH/cortisol release and the behavioral responses following ips apirone challenges were not altered. Our findings suggest that DVP may enhance 5-HT neurotransmission in humans via a subsensitization of 5- HT1A autoreceptors but does not appear to affect postsynaptic 5-HT1A r eceptors. (C) 1997 American College of Neuropsychopharmacology. Publis hed by Elsevier Science Inc.