Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice.

Introduction: Female sexual dysfunction affects approximately 40% of women in the United States, yet few therapeutic options exist for these patients. The melanocortin system is a new treatment target for hypoactive sexual desire disorder (HSDD), but the neuronal pathways involved are unclear. Methods: In this study, the sexual behavior of female MC4R knockout mice lacking melanocortin 4 receptors (MC4Rs) was examined. The mice were then bred to express MC4Rs exclusively on Sim1 neurons (tbMC4RSim1 mice) or on oxytocin neurons (tbMC4ROxt mice) to examine the effect on sexual responsiveness. Results: MC4R knockout mice were found to approach males less and have reduced receptivity to copulation, as indicated by a low lordosis quotient. These changes were independent of body weight. Lordosis behavior was normalized in tbMC4RSim1 mice and improved in tbMC4ROxt mice. In contrast, approach behavior was unchanged in tbMC4RSim1 mice but greatly increased in tbMC4ROxt animals. The changes were independent of melanocortin-driven metabolic effects. Discussion: These results implicate MC4R signaling in Oxt neurons in appetitive behaviors and MC4R signaling in Sim1 neurons in female sexual receptivity, while suggesting melanocortin-driven sexual function does not rely on metabolic neural circuits.

Utilization of behavioral therapy services long-term after traumatic brain injury in young children.

OBJECTIVE: To examine associations of clinical need, defined by elevated parent ratings of child behavior problems and utilization of behavioral health services in young children with traumatic brain injury (TBI) and an orthopedic injury (OI) comparison group. DESIGN: Parents completed outcome measures 18 months after injury and at an extended follow-up conducted an average of 38 months postinjury. SETTING: Children's hospitals and a general hospital. PARTICIPANTS: Participants included parents of 3 groups of children injured between 3 and 7 years of age (N=139): 47 children with complicated mild to moderate TBI, 18 with severe TBI, and 74 with OI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Parents completed ratings of child behavior, mental health symptomology, and family functioning at both visits; at the extended follow-up, they reported utilization of behavior therapy or counseling services since the 18-month follow-up visit. RESULTS: Children with TBI had more behavior problems than those with OI. Although clinical need at both follow-ups was associated with greater service utilization at the extended follow-up, all groups had unmet needs as defined by a clinical need in the absence of services. Lower socioeconomic status was associated with higher rates of unmet need across groups. CONCLUSIONS: The results document unmet long-term behavioral health needs after both TBI and OI in children and underscore the importance of monitoring and treatment of postinjury behavior problems.