Alcohol consumption by young actively growing rats has been previously demonstrated to decrease bone density. This study addresses the mechanism of alcohol action on the early phases of bone growth and development using histomorphometric techniques. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae, including epiphyseal growth plate, were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Trabecular volume and number were greatly reduced in the alcohol-fed animals; however, bone formation rates and mineralization rates were normal. Epiphyseal growth rate and proliferation rate were essentially stopped in the alcohol-fed animals.

Introduction Psychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5-HT). Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, shows promise as a treatment for HSDD. Aim To test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8-OH-DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans. Methods Sexual and social behavior were examined in 8 female marmoset monkeys receiving daily flibanserin (15mg/kg), 8-OH-DPAT (0.1 mg/kg) or corresponding vehicle for 15–16 weeks in a counterbalanced, within-subject design, while housed in long-term, stable male-female pairs. Main outcome measures Marmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8-OH-DPAT or vehicle treatment. 24-h pharmacokinetic profiles of the drugs and their metabolites, as well as drug-induced acute symptoms of the 5-HT behavioral syndrome were also assessed. Results 2-way analysis of variance reveals that flibanserin-treated females attract more male sexual interest (p = .020) and trigger increased grooming (p = .001) between partners. In contrast, 8-OH-DPAT-treated females show increased rejection of male sexual advances (p = .024), a tendency for decreased male sexual interest (p = .080), and increased aggression with their male pairmates (p = .049). Conclusions While 8-OH-DPAT-treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin-treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro-affiliation attributes may underly flibanserin’s effectiveness in treating HSDD in women.

Actively growing rats given 5% alcohol by gavage for 2 days per week have an increased bone length, bone weight, and bone density. The interpretation of these results must be viewed with great caution because studies of chronic alcohol consumption, and many studies of acute drinking, clearly indicate deleterious effects of alcohol on bone health. Those fed alcohol for 5 days per week showed no change.

Given the central role of the decapeptide gonadotropin-releasing hormone (GnRH) in reproductive function, our long-term objective is to delineate the underlying mechanism regulating these reproductive processes. The outcome of GnRH secretion is in part dependent on the proteolytic metabolism of this decapeptide. In contrast to the belief that the metabolism of GnRH serves only as a degradative process that removes excess GnRH, we have shown that a metabolite of the decapeptide, GnRH-(1-5), can directly regulate GnRH gene expression and reproductive behavior. To further characterize the effect of GnRH-(1-5) on GnRH neuronal function, we determined whether GnRH-(1-5) can directly regulate GnRH secretion and pulsatility using an in vitro perifusion system. We compared the effect of GnRH-(1-5) on GnRH secretion in the immortalized GnRH neuron (GT1-7 cell line), whole rat hypothalamic explant, and enzymatically dispersed rat hypothalamic cells. Tissue preparations were perifused continuously for 9 h during which a 3-h challenge with GnRH-(1-5) was administered (4-6 h). The results show that treatment with GnRH-(1-5) increased (p < 0.05) the mean GnRH secretion and the amplitude of the pulses but not the pulse frequency. The present study supports the notion that GnRH-(1-5) is functionally capable of regulating the reproductive neuroendocrine system.