We aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways. Forty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum. DEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group. Darbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.

Hypoxia can adversely affect multiple organ systems. This study investigated the impact of intermittent hypoxia on serotonin levels and depression-like behaviors across distinct neuroanatomical regions. Sixteen adult female Wistar albino rats were divided into two groups: control (n = 8) and hypoxia (n = 8). The hypoxia group was exposed to a simulated altitude of 3000 for 5 h daily over 14 days. Behavioral assessments included locomotor activity (open field test) and depression-like behaviors (forced swimming test). Serotonin levels were quantified via ELISA in the prefrontal cortex, striatum, thalamus, hypothalamus, hippocampus, and serum. Intermittent hypoxia did not alter locomotor activity (p > 0.05) but significantly increased depression-like behavior (p < 0.05), accompanied by a pronounced reduction in swimming behavior (p < 0.0001), a marker associated with serotonergic function. Serotonin levels were significantly reduced in the prefrontal cortex (p < 0.005) and striatum (p < 0.05), while no changes were observed in other regions or serum (p > 0.05). These findings demonstrate that intermittent hypoxia induces depression-like behaviors and region-specific serotonin depletion, particularly in the prefrontal cortex and striatum. This underscores the need to evaluate hypoxia-related brain health implications in conditions such as sleep apnea and acute mountain sickness.

Pregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors. Fifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment. In the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia. Acute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.

Insulin resistance (IR) is described as an impaired response to insulin stimulation of target cells. The present study was designed to investigate the impact of the dexamethasone-induced IR model on self-care behaviors and brain-derived neurotrophic factor (BDNF). Sixteen adult Wistar albino rats were divided into control and IR groups (n = 8). Dexamethasone was administered intraperitoneally at 1 mg/kg/day for 5 days to induce the IR model. Open field and splash tests were performed to evaluate locomotor activity and self-care depression-like behaviors, respectively. BDNF was analyzed by enzyme-linked immunosorbent assay in the striatum and prefrontal cortex (PFC). Shapiro–Wilk, Student’s t-test, and Fisher’s exact test were used as statistical tests. Furthermore, the relationship among homeostasis model assessment of insulin resistance (HOMA-IR), BDNF, and total grooming behavior was analyzed using the Pearson correlation test. Total distance traveled, grooming frequency, and grooming time decreased in the IR group compared to the control group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, and HOMA-IR values increased in the dexamethasone-applied group (P < 0.05). BDNF decreased in the prefrontal cortex in the IR group (P < 0.05). The striatum BDNF level decreased slightly but was insignificant (P > 0.05). Degeneration of the islets of Langerhans in the pancreas, tubular degeneration in the kidney, degeneration of hepatocytes, and mononuclear cell infiltration in the liver increased in the IR group compared to the control group (P < 0.05). PFC BDNF levels, total grooming, and HOMA-IR values displayed a significant correlation (P < 0.05). The PFC was found to be more vulnerable to IR. Our results suggest that IR deteriorates self-care behaviors and the BDNF level of the prefrontal cortex.

Background: Ketamine is a widely used anesthetic agent. Although the potential adverse effects of ketamine use in juvenile age are uncertain, certain studies reported that children exposed to recurrent anesthesia could face an increased risk of neurodevelopmental deficits in motor function and behavioral risks. We aimed to investigate the long-term effects of repeated exposure to various ketamine doses on anxious behavior and locomotor activity in juvenile rats. background: Ketamine is a widely used anesthetic agent. Although the potential adverse effects of ketamine use in juvenile age are uncertain, certain studies reported that children exposed to recurrent anesthesia could face an increased risk of neurodevelopmental deficits in motor function and behavioral risks. Objective: We aimed to investigate the long-term effects of repeated exposure to various ketamine doses on anxious behavior and locomotor activity in juvenile rats. objective: We aimed to investigate the long-term effects of repeated exposure to various ketamine doses on anxious behavior and locomotor activity in juvenile rats. Methods: Thirty-two Wistar Albino juvenile male rats were randomized into 5 mg/kg, 20 mg/kg, and 50 mg/kg ketamine (KET) and saline (Group C) Groups and KET was administered for 3 consecutive days at 3-hour intervals in 3 doses. Ten days after the last KET dose, behavioral parameters were analyzed with an open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB). Statistical analysis was conducted with One-Way ANOVA and Tukey test. method: Thirty-two Wistar Albino juvenile male rats were randomized into 5 mg/kg, 20 mg/kg and 50 mg/kg ketamine (KET) and saline (Group C) Groups and KET was administered for 3 consecutive days at 3-hour intervals in 3 doses. Ten days after the last KET dose, behavioral parameters were analyzed with open field test (OFT), elevated plus maze (EPM) and light dark box (LDB). Statistical analysis was conducted with One-Way ANOVA and Tukey test. Results: Unsupported rearing behavior decreased in 5 and 50 mg/kg KET Groups when compared to Group C. Incorrect transition time, total grooming time, and transfer latency time increased significantly in the 50 mg/kg KET Group when compared to Group C. result: Unsupported rearing behavior decreased in 5 and 50 mg/kg KET Groups when compared to Group C. Incorrect transition time, total grooming time, stretched attend posture, and transfer latency time increased significantly in 50 mg/kg KET Group when compared to Group C. These results suggested that 50 mg/kg KET led to higher anxiety. Light zone time decreased in only 20 mg/kg KET Group, where anxiety was lower. Conclusion: These results suggested that 50 mg/kg KET led to anxiety-like behavior and destroyed memory and spatial navigation. Ketamine doses were associated with late effects of ketamine on anxiety-like behavior in juvenile rats. Further studies are needed to determine the mechanisms that play a role in the different effects of ketamine doses on anxiety and memory. conclusion: Ketamine doses were associated with late effects of ketamine on the anxiety-like behavior in juvenile rats. Further studies are needed to determine the mechanisms that play a role in different effects of ketamine doses on anxiety. other: -