Intra-ventromedial Hypothalamus Blockade of Dopamine Type 2 Receptors by Sulpiride Ameliorates the Fertility-Disrupting Effects of Morphine in Female Wistar Rats

Background and Objective: Polycystic ovary syndrome (PCOS) is a reproductive disorder that causes infertility. Morphine, when injected into the ventromedial hypothalamus (VMH), is effective in inducing PCO, but the mechanism of this effect, particularly concerning dopamine (DA), remains unclear. The study aims to understand how DA and its receptors contribute to this disruption. Materials and Methods: Virgin animals weighing 220-250 g and aged 8-9 weeks were randomly divided into control, morphine alone, sulpiride alone, and sulpiride + morphine groups that received sulpiride before an effective dose of morphine. Morphine (0.1-0.4 μg/rat) was injected into the VMH (AP coordinates: -1.92; ventral: 9 mm; lateral: 0.5 mm). Sulpiride (0.1-0.4 μg/rat) was injected intra-VMH alone or before morphine (0.4 μg/rat, intra-VMH). The control group received saline merely (1 μL/rat, intra-VMH). The animals were anesthetized three days later, and after surgery, the ovaries, uterus, and brain were collected and examined in 10% formalin. All data were statistically analyzed. Results: Ovaries of rats treated with morphine and not in the sulpiride single groups showed PCO features compared to the control group; however, the number of cysts was significantly reduced in the sulpiride + morphine samples. Morphine and sulpiride did not significantly induce uterine inflammation. Moreover, no significant effect on VMH neurons was observed in any of the groups. Conclusion: These results indicate that morphine disrupts follicular growth and that this effect is partially reversed by blocking DA type 2 receptor signaling.