Sex difference alters the behavioral and cognitive performance in a rat model of schizophrenia induced by sub-chronic ketamine.

Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.

Sex difference affects fear extinction but not lithium efficacy in rats following fear-conditioning with respect to the hippocampal level of BDNF.

In rodents, exposure to electrical shock and creating a strong fear memory using fear-conditioning model can induce PTSD-like behavior. In this study, we induced a fear-conditioning model in rats and investigated freezing (PTSD-like) behavior, 21 days after three shocks exposure (0.6 mA, 3 s, 30 seconds interval) in both male and female rats. Lithium was injected intraperitoneally (100 mg/kg) in three protocols: (1) 1 h after fear-conditioning (2) 1 h, 24 h, and 48 h after fear-conditioning (3), 1 h, 24 h, 48 h, 72 h, and 96 h after fear-conditioning. Extinction training (20 sounds without shocks, 75 dB, 3 s, 30 seconds interval) was performed in three protocols: (1) 1 h after fear-conditioning (one session), (2) 1 h, 24 h, and 48 h after fear-conditioning (three sessions), (3), 1 h, 24 h, 48 h, 72 h, and 96 h after fear-conditioning (five sessions). Forced swim test (FST) and hot plate were used to assess behavior. Results showed that lithium in all protocols had no effect on freezing behavior, FST, and pain subthreshold in all rats. Extinction training decreased freezing behavior, with more efficacy in females. In males, only 5-session training was effective, while in females all protocols were effective. Extinction training also altered pain perception and the results of FST, depending on the sessions and was different in males and females. Brain-derived neurotrophic factor (BDNF) mRNA level was increased in females following 3 and 5 sessions, and in males following 5 sessions extinction training. In conclusion, we suggested that there is a sex difference for the effect of extinction training on freezing behavior and BDNF mRNA level in a rat model of fear-conditioning.

Parkinson's Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression.