Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects

Objective: To examine the effects of short-term valproate treatment on human brain serotonin and dopamine function by means of challenge tests with ipsapirone, a partial agonist at 5-HT_1A receptors, and apomorphine, a dopamine receptor agonist. Design: Experimental challenge-rechallenge, within-subjects repeated measures, before and at the end of 14 days of treatment with valproate at a dosage of 625 mg/d (reached gradually over the first 5 days). Participants: Eight healthy male volunteers (mean age 38 years) selected for good physical and mental health who were nonsmokers. Outcome measures: Pharmacological probes were used to evaluate the effects of valproate. In the ipsapirone challenge, changes in adrenocorticotropic hormone (ACTH), cortisol and body temperature were measured, and in the apomorphine chalenge, growth hormone (GH) and prolactin were the dependent variables. Results: Valproate treatment did not significantly alter the ACTH, cortisol or body temperature responses to ipsapirone (20 mg by mouth), which reached equivalent plasma levels at each challenge. Similarly, valproate treatment did not alter the GH or prolactin responses to apomorphine (5 μg/kg subcutaneously). Conclusions: These results suggest that short-term treatment with valproate at a dose of 625 mg/d does not alter hypothalamic or pituitary 5-HT_1A or dopamine receptor responses to challenges with ipsapirone and apomorphine, respectively.