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-HT1A receptors, and apomorphine, a dopamine receptor agonist.


METHODS
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).


METHODS
Eight healthy male volunteers (mean age 38 years) selected for good physical and mental health who were nonsmokers.


METHODS
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 challenge, 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 micrograms/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-HT1A or dopamine receptor responses to challenges with ipsapirone and apomorphine, respectively.
Delva
Nicholas J
NJ
Departments of Psychiatry and Physiology, Queen's University, Providence Continuing Care Centre, Mental Health Services, Kingston, ON. DelvaN@pccc.health.org
Brooks
Deborah L
DL
Franklin
Michael
M
al-Said
Khalid
K
Hawken
Emily R
ER
Merali
Zul
Z
Lawson
J Stuart
JS
Ravindran
Arun V
AV
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001058:Apomorphine / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D006304:Health Status; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D011743:Pyrimidines / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D018491:Dopamine Agonists; D011743:Pyrimidines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D019382:Human Growth Hormone; D014635:Valproic Acid; C043077:ipsapirone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D001058:Apomorphine; D006854:Hydrocortisone