Abstract # 177:

Scheduled for Friday, August 19, 2005 07:00 PM-09:00 PM: (Cambridge/Oxford Room) Poster Presentation

Prior Exposure to Oral Contraceptives Alters Proteins that Synthesize and Degrade Serotonin in the Dorsal Raphe

J. A. Henderson1, C. A. Shively2 and C. L. Bethea1
1OHSU, Division of Reproductive Sciences, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006, USA, 2Wake Forest University
     Oral contraceptives (OCs) alter serotonergic neurotransmission in women and we have previously reported prior OC exposure alters the behavior, hypothalamic-pituitary-adrenal axis and serotonin system in cynomolgus macaques (Macaca fascicularis). In this experiment we investigated the effects of prior OC exposure on proteins involved in the synthesis and degradation of serotonin. Socially living monkeys were administered either a placebo (n=8) or an OC (Triphasil¬©, levonorgestrel and ethinyl estradiol; n = 8) for 26 months. Monkeys were then ovariectomized and 36 months later were necropsied. The brains were processed for Western blot analysis and probed with specific antibodies to tryptophan hydroxylase-1 (TPH), phosphoserine, monoamine oxidase (MAO)-A and MAO-B. Densitometric analysis of signal bands was performed using NIH Image Gel Plotting software and a paired student t-test. Ovariectomized animals previously treated with OCs had higher TPH densities in the dorsal raphe compared to placebo-treated controls (P = 0.001) while phosphoserine levels did not differ (P = 0.73). Previously OC-treated monkeys also had lower MAO-A, but not MAO-B, levels than controls (MAO-A: P = 0.008; MAO-B: P = 0.79). These results suggest prior OC exposure may increase serotonin synthesis and decrease degradation several years after exposure and ovariectomy. These data add to a growing body of knowledge that oral contraceptives have lasting effects on the body, behavior and in the brain, specifically in the serotonin system.