Abstracts

It is well known that valproate (VPA) affects endocrine function. There are, however, contradictory reports in the literature as to whether or not VPA affects the hypothalamic-pituitary-adrenal axis. Such effects, if present, are important since this hormonal axis is crucial in the homeostasis of fundamental bodily functions and in regulation of stress responses. In the present study the effects of VPA exposure on basal and stress-induced cortisol was investigated in male adolescent goats., Twenty-three bucks aged 2 months at the start of experiment were given VPA mixture (n=16) or control solution (n=7) perorally twice daily for 8 months. VPA mixture was given in single doses up to 62.5 mg/kg to sustain therapeutic plasma concentrations (300-600 [micro]mol/l). In [italic]Experiment 1[/italic], blood samples were analyzed for cortisol weekly from weeks 35 to 50 of the year. In [italic]experiment 2[/italic], bucks aged 9 months were exposed to a period of mild stress associated with blood sampling from indwelling jugular vein catheters every 15 minutes for 7 hours. The effects of VPA on plasma cortisol concentration were studied in repeated measured mixed model analyses., VPA treated bucks in [italic]experiment 1[/italic] had significantly lower basal cortisol concentrations than control animals during the study period (F[sub]1,14[/sub]=6.22, p=0.026). A significant time effect (F[sub]7,98=[/sub]5.92, p[lt]0.0001) was found with a decrease in basal cortisol plasma concentrations towards the end of the study period. A significant time/treatment interaction (F[sub]7,98[/sub]=2.63, p=0.016) was found with a more pronounced decrease in plasma cortisol in the control group than in the treated group. In [italic]experiment 2[/italic] the cortisol response to mild stress was different in the VPA group compared to control. Overall, there was a lower cortisol response in the VPA group compared with controls. Mean basal plasma cortisol concentration was 2 ng/ml in both groups. During the first period of mild stress plasma cortisol concentration in the control group was 4-8 ng/ml compared to 3-6 ng/ml in the VPA group. In both groups cortisol decreased after 1.5 hours of blood sampling. The group difference was significant when only main effects were included in the model (F[sub]1,14[/sub]=47.2, p[lt]0.0001)., VPA exposure was associated with a significant reduction in both basal and stress-induced plasma cortisol concentration in male adolescent goats. The observed effects can be a potential problem with long-term VPA treatment. On the other hand, it may be speculated that the reduction in cortisol levels and reduced response to mild stress could be related to the mood stabilizing effect of VPA.,