Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests, the effects of the combined treatment were similar to those of exercise alone, suggesting that exercise is the main factor in the beneficial effects of the combined therapy in PTSD patients.

Glucocorticoid-induced impairment of long-term memory retrieval in female rats: influences of estrous cycle and estrogen.

Using an inhibitory avoidance (IA) task, the effects of glucocorticoids on memory retrieval in intact and ovariectomized (OVX) female rats were investigated. Young adult female rats were trained in a one trial IA task (1-mA, 3-s footshock). The latency to reenter the dark compartment of the apparatus was recorded in the retention test performed 48h after training. Pre-retrieval injection of corticosterone (CORT, 1, 3, and 10mg/kg) to OVX rats impaired memory retrieval at all doses tested. Similar administration of CORT (3mg/kg) in intact female rats impaired memory retrieval in the estrus phase (when endogenous plasma levels of estrogen are low) but not in the proestrus phase (when endogenous levels of estrogen are high). Concurrent administration of CORT (3mg/kg) and 17-ß-estradiol (15µg/kg) in both proestrus and estrous phases impaired memory retrieval. Our findings indicate that the effects of corticosterone on memory retrieval are modulated by the estrous cycle and 17-ß-estradiol.