| Abstract |
Organisms face stressful conditions and respond to them through the activation of several endogenous systems, such as the Hypothalamus-Pituitary-Adrenal axis HPA axis is highly regulated by Corticotropin Releasing Factor (CRF). CRF-expressing neurons in hypothalamus and other brain regions are activated following stressful stimuli and release CRF. CRF binds to and activates CRF1 receptors in the PFC. Evidence shows the ability of CRF to improve learning and memory; however, findings emphasize the differential effects of stress in male and female anxiety and cognitive functioning. Thus, we investigated the effects of acute restraint stress and the effects of CRF receptor activation on the anxiety and medial-PFC cognitive functions in male and female C57BL/6 mice. Male and female animals were either subjected in 2hour acute Restraint Stress (RS) conditions or remained in their home cage prior to the Light-Dark and Temporal Object Recognition (TOR) tasks. Further to the enquiry, another group of male and female mice were stereotactically implanted with a guide cannula in the Prelimbic PFC. In addition, a non-selective CRF receptor antagonist [(α-helical CRF (9-41)] was injected into the Prelimbic PFC of a subgroup of cannula-implanted animals immediately after the acute RS. In the Light-Dark test, RS female mice spent significantly less time in the dark compartment than the No-Restraint (NoRS) mice (p=0,004), while no such effect was found in male NoRS-RS groups comparison. The Discrimination Index (DI) of the male RS mice was significantly lower than that of the NoRS male mice in the TOR task (p=0,05), while the DI of NoRS and RS female mice was comparable. Dark/Light Index and DI of male control NoRS and cannula-implanted NoRS mice did not differ significantly. Regarding the α-helical CRF (9-41) effects, both NoRS and RS male α-helical injected mice showed similar DI, indicating the ability of α-helical to block the RS-induced memory performance. The female α-helical injected RS mouse spent less time in the dark compartment compared to the female control RS group. No effect of estrous cycle was found in these experiments. In conclusion, we showed the restraint stress-induced anxiety in the RS female group, and the impaired DI of the male RS mice. Future studies should unravel the effects of α-helical CRF (9-41) injection on anxiety and stress-induced cognitive dysfunctions gathering data from a greater number of experimental animals.
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Effects of corticotropin releasing factor antagonists on anxiety-like behavior and prefrontal cortex -related cognitive functions in male and female mice
