The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression

Objective The aim of this study was to investigate the relationship between plasma glutamate, glutamine and gamma-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. Methods The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n= 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. Results The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. Conclusion Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control

Evaluation of the Effect of Prazosin Treatment on alpha-2c Adrenoceptor and Apoptosis Protein Levels in the Predator Scent-Induced Rat Model of Post-Traumatic Stress Disorder

The predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks alpha-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and alpha-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on alpha-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and alpha-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions

Effects of tamoxifen and glutamate and glutamine levels in brain regions in repeated sleep deprivation-induced mania model in mice

Protein kinase C inhibitor tamoxifen reduces symptoms of acute mania in bipolar patients and mania-like behaviors in animals. Memory impairment and altered levels of glutamate and glutamate/glutamine ratio have been reported in mania. Tamoxifen suppresses glutamate release which plays an important role in memory. The present study evaluated whether tamoxifen's activity participates in its antimanic efficacy in repeated sleep deprivation mania model. Mice were divided into control and 24-h sleep-deprived groups and were treated with vehicle or 1 mg/kg tamoxifen twice daily for 8 days. Sleep deprivation was repeated three times at intervals of 2 days. Square crossing and rearing were recorded as measures of locomotor activity. Memory and risk taking behavior were evaluated using novel object recognition and staircase tests, respectively. Glutamate and glutamine levels were measured in the frontal cortex and hippocampus. Behavioral tests were conducted 24 h after the second or immediately after the third sleep deprivations. Sleep deprivation increased locomotor activity and risk taking. Glutamate and glutamine levels and glutamate/glutamine ratio in the frontal cortex and hippocampus were unaffected. Locomotor hyperactivity was prevented by tamoxifen treatment. No change in the recognition index suggested lack of memory impairment in the model. These findings confirm the relevance of repeated sleep deprivation as a mania model and tamoxifen as an antimanic agent. However, future research is needed to further address lack of memory impairment in the model and lack of glutamatergic influence on the model and antimanic effect of tamoxifen