Relaxin 3 and sex differences in post-stroke depression

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Every year in the United States over 600,000 people experience their first stroke. Indeed, stroke is the 4th leading cause of death in the U.S. and one of the leading causes of long-term disability. There are significant sex differences in the epidemiology of stroke as well as the neurological and functional outcomes following stroke. Overall, men have a higher prevalence of stroke while women have poorer outcomes. One consequence that is reported in both men and women is the onset of post-stroke depression, although it is more common in women. Post- stroke depression is associated with significant long-term disability and often interferes with rehabilitation efforts. In spite of the pervasiveness of post-stroke depression and the negative impact of depression on long-term outcomes, few animal models have investigated the development of depressive-like behaviors post stroke. Relaxin 3 is a highly conserved neuropeptide that modulates a number of behaviors with data suggesting both anxiolytic and anti-depressant properties. Importantly, the relaxin 3 system demonstrates significant sex differences. The purpose of the current proposal is to examine the development of post-stroke depression using well-validated measures of anhedonia and effort-based responding in male and female rats (Specific Aim 1). In addition, these studies will also examine the sex-specific effects of ischemic stroke on the relaxin 3 system and will investigate the efficacy of relaxin 3 as a novel therapeutic in post-stroke depression (Specific Aim 2). Together, these studies will determine sex-specific effects of stroke-induced changes in affective behaviors with an emphasis on incentive motivation and the potential role of the neuropeptide relaxin 3 in the expression of depressive-like behaviors.