Modulation of Melatonin Receptors Regulates Reproductive Physiology: The Impact of Agomelatine on the Estrus Cycle, Gestation, Offspring, and Uterine Contractions in Rats.

Agomelatine is a pharmaceutical compound that functions as an agonist for melatonin receptors, with a particular affinity for the MT1 and MT2 receptor subtypes. Its mode of action is integral to the regulation of diverse physiological processes, encompassing the orchestration of circadian rhythms, sleep-wake cycles, and mood modulation. In the present study, we delve into the intricate interplay between agomelatine and the modulation of estrus cycles, gestation periods, offspring numbers, and uterine contractions, shedding light on their collective impact on reproductive physiology. Both in vivo and in vitro experiments were performed. Wistar Albino rats, divided into four groups: two non-pregnant groups (D1 and D2) and two pregnant groups (G1 and G2). The D1 and G1 groups served as control groups, while the D2 and G2 groups received chronic agomelatine administration (10 mg/kg). Uterine contractions were assessed in vitro using myometrial strips. Luzindole, a melatonin receptor antagonist, was employed to investigate the pathway mediating agomelatine's effects on uterine contractions. In in vivo studies, chronic agomelatine administration extended the diestrus phase (p<0.05) in non-pregnant rats, prolonged the gestational period (p<0.01), and increased the fetal count (p<0.01) in pregnant rats. Additionally, agomelatine reduced plasma oxytocin and prostoglandin-E levels (p<0.01) during pregnancy. In vitro experiments showed that agomelatine dose-dependently inhibited spontaneous and oxytocin-induced myometrial contractions. Luzindole (2 µM) reverse the agomelatine-induced inhibition of myometrial contractions. These findings suggest that agomelatine holds the potential to modulate diverse reproductive parameters during the gestational period, influencing estrus cycling, gestational progression, offspring development, and the orchestration of uterine contractions.

Effects of treadmill exercise on sexual behavior and reproductive parameters in chronically stressed-male rats.

Exposure to chronic stress stimulates the hypothalamic-pituitary-adrenal (HPA) axis and then simultaneously inhibits hypothalamic-pituitary-gonadal axis (HPG) axis activity. The inhibition formed by the HPA axis is the main mechanism of action of stress on reproductive function. HPG axis activity is known to be changed by various factors, including exercise. Exercise has been found to have a number of positive effects on sexual behavior, reproductive hormones, and sperm parameters in studies with animal models for many years. The main aim of this study is to investigate the effects of chronic treadmill exercise on chronically stressed-male rats' sexual behavior, reproductive hormones, and sperm parameters. A total of 40 sexually adult male rats were randomly and equally divided into four groups as control, stress, exercise, and stress+exercise. Animals in the exercise group were subjected to the chronic treadmill exercise (moderate intensity) for 33 days with a periodic increase in speed and duration. Animals in the stress group were exposed to restraint stress for 1 h, 2 h, and 3 h during the first, second and third 15 days respectively. Sexual behavior parameters, hormone measurements, and sperm parameters were evaluated. The main effects of chronic exercise on sexual behavior were centered on a significant increase in the ejaculation frequency (EF) in the stress+exercise group. Also, sperm concentration and motility in the stress group significantly decreased, and then sperm motility was improved by exercise in the stress+exercise group. In sum, our results show that chronic treadmill exercise may improve the adverse effects of chronic stress on sexual behavior and sperm parameters in male rats in terms of some parameters.

The effects of lipopolysaccharide-induced endogenous hyperthermia and different antipyretic treatment modalities on rat brain.

BACKGROUND: In the present study, the effects of fever and hyperthermia, and different anti hyperthermia treatment modalities on the brain by was investigated by using experimental animal model MATERIALS AND METHODS: Endogenous hyperthermia (41 degrees C) was induced by lipopolysaccharide (LPS) injection, and the signs of probable neuronal damage were evaluated by healthy, necrotic and apoptotic cells, and heat-shock proteins (HSP 27 and HSP 70) in cerebral cortex, cerebellum and hypothalamus. The animals were treated with widely used treatment modalities for high fever in pediatric practice, namely hypothermia, dexamethasone, paracetamol and diclofenac, and their effect on the hyperthermia-induced brain changes were evaluated. RESULTS: Generalized seizure was observed in fifteen rats of which rectal temperature achieved 41 degrees C (15/36, 41%); five of them died on second day (5/15, 33%). LPS-induced endogenous hyperthermia; (i) caused significant increase of necrotic cells in cerebral cortex and cerebellum and apoptotic cells in all three regions (p < 0.05), (ii) caused significant decrease of healthy cells in cerebral cortex (p < 0.05), and (iii) no significant change of HSP 27 and 70 in all three neuronal locations (p > 0.05). For the treatment modalities applied; (i) paracetamol had an effect of increasing the healthy cell count in cerebral cortex and hypothalamus and decreasing the necrotic cell count in cerebellum and hypothalamus (p < 0.05). CONCLUSION: The neuronal tissue in different regions of brain can show various degrees of damage in response to endogenous hyperthermia and the applied medications have varying degree of protection (Tab. 3, Fig. 6, Ref. 44).