THE 2012 NAGS/PROQUEST DISTINGUISHED DOCTORAL THESIS AWARD:

Patricia J. Allen, Tufts University
Advisor: Robin B. Kanarek, Ph.D.

Sex-dependent effects of chronic creatine supplementation on depression-like behavior in the rat forced swim test

Athletes and body builders use creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the critical role creatine plays in brain function. The ability of creatine to enhance cognitive behavior is garnering attention as a novel strategy for the treatment of depressive disorders. In humans, creatine supplementation improves mood in treatment-resistant depression and may alter brain chemistry in a manner that increases the likelihood of response to antidepressant treatment. For this thesis project, four experiments evaluated the effects of chronic creatine supplementation on depression-like behavior using the rat forced swim test (FST), an animal model sensitive to antidepressants with clinical efficacy in humans. For all experiments, rats were maintained on either chow or chow blended with 2% w/w or 4% w/w creatine monohydrate for five weeks prior to the FST. In experiments 3 and 4, creatine was combined with sub-acute treatment with Prozac, a commonly used antidepressant. Body weight, water intake, and calorie consumption were recorded daily and to gauge the behavioral specificity of creatine on depression-like behavior, tests measuring exploration and coordination were performed within a week after the FST. In all experiments, creatine altered depression-like behavior in the FST in a sex-dependent manner. Specifically, creatine increased depression-like behavior in male rats and decreased depression-like behavior in female rats. However, creatine did not enhance the effect of a sub-optimal dose of fluoxetine. Ongoing studies intend to clarify the nature of sex differences in response to creatine. Sexual dimorphism in brain creatine is intriguing particularly in light of sex differences in the incidence of depression. Insight into the neural mechanisms underlying these sex differences may profoundly affect our understanding of the role of creatine in the brain and potentially lead to sex-specific therapeutic strategies in the treatment of depression.