The effects of current and prior oral contraceptive treatment on the behavior and neurobiology of cynomolgus monkeys

Oral contraceptives (OCs) are the most widely prescribed and effective of the reversible contraceptive methods. OC use is associated with a plethora of peripheral changes, some of which have been shown to persist after cessation of usage. OCs also alter central nervous system (CNS) function in women resulting in changes in the physiological response to stress, perception, cognition, libido and affect. Due to the inherent difficulties of CNS investigation in human beings, very little research has been directed at characterizing the effects of OCs on the neurotransmitter systems that may underlie these changes. Therefore, the studies comprising this dissertation were designed to investigate the effects of one currently marketed OC formulation on the CNS in cynomolgus monkeys.; The first series of experiments investigated the effects of one OC formulation on behavior, hypothalamic-pituitary-adrenal (HPA) function and the CNS response to challenge. The results of these studies suggest that OC treatment disrupted social behavior, HPA axis regulation and the underlying CNS function. These effects were also observed one year after discontinuation of OCs and ovariectomy.; Given that several peripheral and CNS changes persist after discontinuation of OC treatment, it seems reasonable that other OC-induced changes may also be long-term. Thus, the second study investigated the effects of prior OC treatment on global cognitive function, using a problem-solving task. The findings from this study suggest that prior OC treatment may impair cognitive performance for at least a year after cessation of treatment.; The third study investigated the effects of prior OC treatment on the serotonin system in the dorsal raphe and anterior striatum. The results of these receptor autoradiography studies suggest that OCs had lasting effects due, in part, to alterations in receptor and transporter density.; Together, the data presented in this dissertation suggest that OCs produce lasting changes in the CNS, specifically in the serotonin system. The existence of residual effects on the CNS makes a woman's decision to take OCs more significant. Further investigations of OC-induced changes in monoaminergic function and their significance in the behavioral and psychological side effects produced by OCs are needed.