Objective: The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial. Methods: In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons. Results: Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented. Conclusion: Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied.

Aim: To our knowledge; this is the first study that compared the efficacy and safety of aripiprazole 1-month and paliperidone 1-month and paliperidone 3-month long-acting forms preparations as well as plasma drug levels during the maintenance treatment of schizophrenia in the real world. Method: In our study, subjects were evaluated every month for four months with relevant psychiatric measures and plasma drug levels. Follow-up days were determined as days 0, 30, 60, and 90. Plasma drug levels of the treatments were analyzed by using LC/MS-MS. Results: No superiority was observed between the groups regarding PANSS positive and general psychopathology (p>0.05). It was observed that PANSS negative and total scores were statistically lower in the aripiprazole once-monthly group than in the paliperidone 3-month preparations (p<0.05). We observed that Quality of Life Scale interpersonal relations scores, the aripiprazole 1-month group exhibited higher scores than both of the paliperidone groups. Aripiprazole 1-month group scored higher than the paliperidone 1-month group in the intrapsychic foundations subscale (p<0.05). No significant difference was observed between extrapyramidal adverse effect, akathisia, and insight levels among the three groups (p>0.05). Aripiprazole 1- month group scored significantly lower than both paliperidone groups in the Arizona Sexual Experiences Scale (p<0.001). Aripiprazole metabolite was negatively correlated with depressive symptoms in the Calgary Depression Assessment Scale in Schizophrenia (p<0.05) and the Barnes Akathisia Rating Scale (p<0.05). Conclusion: Aripiprazole once-monthly showed superiority in efficacy aspects to PP3M but not PP1M and similar safety with both paliperidone formulations.

Objective: Glutamate-induced excitotoxicity has a role in the pathophysiology of neurodegenerative disorders. Lamotrigine, an antiepileptic drug, also used to treat bipolar disorders, may be protective against excitotoxic insult. The aim of the study was to investigate the neuroprotective effect of lamotrigine against the glutamate excitotoxicity in SH-SY5Y cell line. Materials and Methods: SH-SY5Y human neuroblastoma cells were pre-treated with lamotrigine (50-100-150 µM) prior to exposure to 15 mM glutamate. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to determine cell viability. The anti-oxidant effect of lamotrigine and the role of inflammatory parameters were determined by measuring superoxide dismutase (SOD), hydrogen peroxide (H 2 O 2), IL-1β, IL-6 and TNF-α. Results: Intracellular calcium levels and lactate dehydrogenase (LDH) activity increased in glutamate exposed cells. Pre-treatment of cells with MK-801 showed no protective features against glutamate excitotoxicity. Treatment with 100 µM lamotrigine was effective in increasing the viability of glutamate exposed cells and in reducing H 2 O 2 increase in these cells. The SOD activity increased by lamotrigine treated cells exposed to glutamate. IL-1β, IL-6 and TNF-α levels increased after induction with glutamate and attenuated by lamotrigine. Conclusion: Overall, our results confirmed the critical role of inflammation and oxidative stress in glutamate-induced excitotoxicity and lamotrigine may exert a protective effect.

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BACKGROUND: Rational pharmacology use and appropriate prescribing are among the key learning outcomes in medical education. Some medical faculties include rational pharmacotherapy course in their education programs at different years of education in Turkey. The aims of this study were to investigate the differences in effect of rational pharmacotherapy course on short- and long-terms by comparing two cohorts who attended the course in different clinical years of medical education by identifying which parameters of prescription items are different among groups. MATERIALS AND METHODS: This quasi-experimental study was conducted in School of Medicine. Participants consisted of 157 students who attended the course in Grade 4 (n = 110, Group A) and Grade 5 (n = 47, Group B). Students were asked to complete a prescribing task both upon completion of the course and 1 year after. The performance in prescribing was determined by prescription scoring form. Repeated measures ANOVA was employed to test the intervention effect between two periods. McNemar test was employed to measure the change in each item on the prescription. Point-biserial correlations between each item on the prescription and their scores on the test as a whole were calculated. RESULTS: The mean score of Group A dropped to 59.41 (standard deviation [SD] = 14.06) from 90.43 (SD = 8.90), and the mean score of Group B dropped to 73.37 (SD = 12.56) from 83.91 (SD = 10.03). All the prescription components in the scripts of the Group A students worsened significantly, except the “name of drug,” whereas Group B students maintained most of them after 1 year. CONCLUSIONS: This study shows that the long-term retention effect of rational pharmacotherapy course conducted in later years of education is better than the course conducted in earlier years of education, which may be related to the fact that students in later years are more likely to take on responsibility for patient therapy process in clinical education.