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-HT1A receptor agonist ipsapirone are considered to provide an index of 5-HT1A receptor function in humans. To examine the effects of divalproex sodium (DVP) on 5-HT1A receptor function in humans, we measured the hypothermic, adrenocorticotropic hormone (ACTH) cortisol, and behavioral responses to ipsapirone in 10 healthy male volunteers. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained at regular intervals for three hours. The ipsapirone challenge tests were repeated after the subjects had been treated with DVP (1000 mg/day) for one week. The results showed that the hypothermia induced by ipsapirone was significantly attenuated by the DVP treatment, whereas the ACTH/cortisol release and the behavioral responses following ipsapirone 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 receptors.
Shiah
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Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Yatham
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Lam
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Zis
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D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology*
D018692:Antimanic Agents; D006728:Hormones; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014635:Valproic Acid; C043077:ipsapirone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone