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Objectives: Activation of neuronal nitric oxide synthase (nNOS) and interrelated alterations of calmodulin and ionotropic glutamate receptor (GluN1) levels are unknown in post traumatic stress disorder (PTSD). Materials and Methods: Sprague-Dawley rats of both sexes were exposed to dirty cat litter, and then placed on an elevated plus maze. An anxiety index was calculated and tissue samples from hippocampus and amygdala were prepared in order to detect calmodulin, NOS and GluN1 by immunoblotting. Results: The anxiety indices of the traumatized rats were markedly higher than those of the controls (p<0.05). GluN1 and calmodulin levels were decreased in the dorsal hippocampus and amygdaloid complex of the traumatized rats. NOS expression increased significantly in both the amygdaloid complex and dorsal hippocampus where the increase was statistically more prominent in the amygdaloid complex (p< 0.001) than in the dorsal hippocampus of the traumatized rats (p<0.05). Conclusion: Predator exposure in rats causes long-lasting anxiogenic effects associated with increases in NOS and decreases in GluN1 expressions in brain areas related to PTSD symptoms and excitotoxicity. The results suggest that excitotoxicity occurs through other mechanisms rather than GluN1 receptors. [ABSTRACT FROM AUTHOR]

Objective: The B-cell lymphoma/leukemia-2 (Bcl-2) family of proteins governs mitochondrial membrane permeability where the programmed apoptotic process is controlled by the balance between proapoptotic (Bax) and antiapoptotic (Bcl-2) proteins. We aimed to investigate the [Bcl-2]/[Bax] in different brain regions in a post-traumatic stress disorder rat model. Methods: Female Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter) in reversed 12 h light/dark cycle. The rats received intraperitoneal saline, fluoxetine (2.5 mg/kg/day) or propranolol (10 mg/kg/day) for 7 days between exposure sessions. Following exposure to the trauma reminder, elevated plus maze experiments were done. Immunoblotting was used to quantify [Bcl-2] and [Bax] proteins in the homogenates of the dorsal hippocampus, the frontal cortex and the amygdaloid complex. Results: Fluoxetine reversed the increases in the anxiety indices and the freezing times. In the amygdaloid complex and the frontal cortex, the [Bcl-2]/[Bax] decreased in the traumatized control rats significantly (p<0.0001), but not in the dorsal hippocampus. Although the fluoxetine treatment reversed the apoptotic changes but propranolol failed and caused proapoptotic proteins to increase. Conclusion: These results may suggest a neuroprotective role for fluoxetine but not for propranolol. [ABSTRACT FROM AUTHOR]

Abstract: This study shows the possible contribution of muscarinic receptors in the pathophysiology of post-traumatic stress disorder. Sprague-Dawley rats of both sexes were exposed to dirty cat litter (trauma) for 10min and the protocol was repeated 1 week later with a trauma reminder (clean litter). The rats also received intraperitoneal fluoxetine (2.5, 5 or 10mg/kg/day), propranolol (10mg/kg/day) or saline for 7 days between two exposure sessions. Functional behavioral experiments were performed using elevated plus maze, following exposure to trauma reminder. Western blot analyses for M1, M2, M3, M4 and M5 receptor proteins were employed in the homogenates of the hippocampus, the frontal cortex and the amygdaloid complex. The anxiety indices increased from 0.63±0.02 to 0.89±0.04 in rats exposed to the trauma reminder. The freezing times were also recorded as 47±6 and 133±12s, in control and test animals respectively. Fluoxetine or propranolol treatments restored the increases in the anxiety indices and the freezing times. Female rats had higher anxiety indices compared to males. Western blot data showed increases in M2 and M5 expression in the frontal cortex. Expression of M1 receptors increased and M4 subtype decreased in the hippocampus. In the amygdaloid complex of rats, we also detected a down-regulation of M4 receptors. Fluoxetine and propranolol only corrected the changes occurred in the frontal cortex. These results may imply that muscarinic receptors are involved in this experimental model of post-traumatic stress disorder. [Copyright &y& Elsevier]