Ovulation is a critical event in mammalian reproduction, a complex process that involves the release of a mature oocyte from the ovaries for fertilization. Hormonal shifts are the driving force of the ovulation cycle; however, several other factors are able to fine-tune the occurrence of follicular rupture. Prior to the follicular rupture, the pre-ovulatory luteinizing hormone (LH) surge triggers a self-generating local inflammatory and redox cascade, which is responsible for the release of several inflammatory and redox signaling mediators. Eicosanoids are one of the key regulators of the initiation of the local inflammation within the follicle, while the balance of reactive oxygen species and antioxidants is fundamental to maintaining the physiologically coordinated redox state during the ovulation process. In this review, we aim to provide a summary of the human menstrual and rat estrus cycles and demonstrate the LH-induced inflammatory and redox cascade involved in follicle rupture through the details of lipid-derived and redox signaling mediators.

The limited efficacy of antipsychotics in treating the negative and cognitive symptoms of schizophrenia has prompted the exploration of adjuvant therapies. Several drugs developed for other indications—including caffeine, metformin, and furosemide—have shown procognitive potential. This study evaluated the effects of these agents on behavioral parameters using the reward-based Ambitus test, and on the cerebral D2 dopamine receptor (D2R) expression and binding. The drugs were administered individually and in combination in a schizophrenia-like triple-hit animal model (Lisket rats), derived from the Long Evans (LE) strain. Lisket rats received 14 days of drug treatment via drinking water; water-drinking LE rats served as the controls. The Ambitus test was conducted before treatment and on days 11–14. Caffeine enhanced activity without affecting learning or memory. Metformin and furosemide reduced exploratory behavior but improved reference memory; these effects were inhibited by caffeine co-administration. Although no statistically significant behavioral differences were found compared to water-treated Lisket rats, a trend toward reduced exploratory visits was observed in the triple-combination group. Lisket rats exhibited moderately reduced D2R binding in the cortex and increased binding in the hippocampus. Caffeine alone and in combination enhanced hippocampal D2R binding, while furosemide increased cortical D2R expression. This study is the first to highlight the behavioral and molecular effects of these non-antipsychotic agents in a schizophrenia model, supporting their potential for adjunctive use.