The Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-induced Cognitive Impairments in Mice.

BACKGROUND:  Glutamatergic N-methyl-D-aspartate (NMDA) receptors play vital roles in memory formation. Changes in the activity of these receptors influence memory processes. Ketamine is a noncompetitive NMDA receptor antagonist drug with promising mood-altering and pain-reducing effects in low doses. These effects are believed to be related to altered serotonergic transmission. METHODS:  The present study investigated the involvement of the serotonergic system in low-dose ketamine administrations' effects on memory acquisition, consolidation, and retrieval processes. Sixty-four male BALB/c mice were used in this experiment and separated into 8t groups. Mice were treated subchronically with a selective serotonin reuptake inhibitor, fluoxetine, and a serotonin depletion agent, p-chlorophenylalanine (pCPA). A serotonin antagonist, methiothepin, and ketamine were acutely administered 60 minutes before or after the behavioral tests. A passive avoidance (PA) test measured emotional memory acquisition, consolidation, and retrieval processes. Hippocampi malondialdehyde (MDA) levels were analyzed, and histopathological examinations were performed. RESULTS:  Ketamine alone did not significantly affect memory encoding processes in the PA test, while the ketamine-fluoxetine combination disrupted memory consolidation. Fluoxetine negatively affected the memory acquisition process, which was normalized during the consolidation and retrieval trials. Drug applications did not significantly alter hippocampal MDA levels. In all ketamine-applied groups, histopathologic alterations were evident. CONCLUSION:  Low-dose ketamine administration induces neurodegeneration, and it also impairs memory functions when combined with fluoxetine, indicating increased serotonergic transmission may be involved in the memory-impairing and neurotoxic effects of ketamine.

A case-control study on depression, anxiety, and belief in sexual myths in trans women.

Objective: The purpose of our study was to investigate depression, anxiety, and belief in sexual myths in trans women. Methods: This is a prospective case-control study. The case group included 60 trans women who were referred to the Medical Biology and Genetics Department from various clinics of the research and training hospital where this study was conducted. The control group consisted of 60 healthy male individuals who presented to the same hospital for routine health follow-ups and collecting documents showing their health. In data collection, we used a Personal Information Form, the Sexual Myths Scale, and the Beck Depression and Anxiety Inventories. The IBM Statistical Package for the Social Sciences 25.0 was used to analyze the data. Results: In the case group, 26.7% of the participants were sex workers, and all were single. While 46.7% of the participants in the case group were living with their families, 66.7% were smokers, and 13.3% were receiving hormone treatment. All 60 participants in the control group were also single. The participants in the control group had higher levels of believing sexual myths and lower levels of anxiety and depression than those in the case group (p = 0.000). The mean scores of the participants in the control group in the Sexual Orientation and Sexual Violence subscales of the Sexual Myths Scale were higher than the mean scores of those in the case group (p < 0.05). Conclusion: The trans women who participated in this study had higher levels of anxiety and depression and lower levels of believing sexual myths than the control group. The mental health of trans women can be disrupted due to various treatments they are exposed to in society such as stigma, discrimination, and violence. Their higher anxiety and depression levels in this study could be explained by this exposure. This exposure could also have led to their lower total scores in the Sexual Myths Scale, as well as lower scores in the Sexual Violence and Sexual Orientation subscales.

Trolox is more successful than allopurinol to reduce degenerative effects of testicular ischemia/reperfusion injury in rats.

INTRODUCTION: Reperfusion surgery following testicular ischemia is a reproductive health threatening status and may result with organ dysfunction in men. The high level of reactive oxygen species (ROS) and cease of blood flow to the testis are the most important reasons of this testicular injury. Until today, numerous experimental studies reported that antioxidants might be efficient to alleviate oxidative stress induced organ dysfunction. For this purpose, in this study, we have investigated the protective effects of xanthine oxidase (XO) inhibitor, allopurinol, and ROS scavenger, trolox, in a comparative perspective in testicular ischemia reperfusion injury subjected rats. MATERIALS AND METHODS: Twenty-eight adult male Sprague Dawley rats were divided into four groups of seven animals in each; control, ischemia/reperfusion (I/R), allopurinol and trolox. The rats in control group did not receive any application. Animals in I/R, allopurinol and trolox groups were subjected to 2 h testicular reperfusion injury following 5 h ischemia. Intraperitoneally (i.p.) 1 ml isotonic, 200 mg/kg allopurinol and 50 mg/kg trolox were administered to the animals in these groups 30 min prior reperfusion. At the end of experiment, all animals were sacrificed and blood serum malondialdehyde (MDA) levels were measured. Histological sections were obtained from the testis and stained with hematoxylin and eosin (H&E), proliferating cell nuclear antigen (PCNA) and cleaved caspase-3. Apoptotic index was evaluated with TUNEL Assay. RESULTS: Severe morphological degenerations, increased serum MDA, cleaved caspase-3 and TUNEL Assay positivity rate, but reduced PCNA positivity rate was observed in ischemia and reperfusion group. Morphological degenerations, MDA level, apoptotic index and PCNA positive cell rate were slightly alleviated in allopurinol administered animals compared with ischemia and reperfusion group. Protection with trolox was more successful and the results of the analysis were similar to the control group. DISCUSSION: Ischemia that leading to testicular torsion is a reproductive health affecting problem and current surgical treatment methods might be insufficient to recover testis. Various types of ROS generating mechanisms in cell are limiting protective potency of allopurinol, and cocktail administration of different ROS inhibitors might be more effective. However, our results indicate that free radical scavenger trolox might be a candidate drug to alleviate degenerative effects of testicular ischemia reperfusion injury. CONCLUSIONS: This is the first study that demonstrates antioxidant trolox was more successful than XO inhibitor allopurinol to protect testis against ischemia and reperfusion injury in rats.

Exenatide treatment exerts anxiolytic- and antidepressant-like effects and reverses neuropathy in a mouse model of type-2 diabetes.

BACKGROUND: Comorbid neurobehavioral disturbances and type-2 diabetes mellitus (T2DM) warrant immediate research attention. Exenatide, which is a potent and selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the treatment of T2DM. Exenatide displays a multitude of effects in the central nervous system. The aim of this study was to investigate the anxiolytic- and antidepressant-like effects and analgesic effects of exenatide in a type-2 diabetic mouse model. MATERIAL/METHODS: Modified elevated plus-maze test for anxiolytic-like, forced swimming test for depression-like behavior and hotplate test for neuropathy were used as behavioral tasks. Behavioral parameters were investigated in a streptozocin--(100 mg/kg, i.p.) and nicotinamide--(240 mg/kg, i.p.) induced type-2 diabetic mouse model. Exenatide (0.1 µg/kg, s.c., twice daily) was administered for 2 weeks. Vehicle (control), diabetic, and exenatide-treated diabetic mice were tested. RESULTS: Our results confirm that exenatide exerts anxiolytic- and antidepressant-like effects and might be effective in diabetic neuropathy in a diabetic mouse model. CONCLUSIONS: Exenatide may be a good candidate as a treatment option for depression, anxiety, and neuropathy in patients with type-2 diabetes.