Research reportPutative genes mediating the effects of orexins in the posterior paraventricular thalamus on neuroendocrine and behavioral adaptations to repeated stress

Exposure to repeated stress is often associated with psychopathology. However, our understanding of the underlying neural circuitry that regulates responses to repeated stress is limited. The posterior paraventricular thalamus (pPVT) is a brain region responsible for transmission of multimodal sensory information to limbic structures that regulate responses to both acute and repeated stress. Orexin-containing cells originating in the hypothalamus heavily innervate the pPVT. Our previous work has shown that activation of orexin1 receptors in the pPVT during repeated swim stress is important for facilitation of the hypothalamic-pituitary-adrenal (HPA) axis response to subsequent novel restraint. However, the genes responsible for these orexin-mediated adaptations to repeated stress are not known. Using a custom PCR array we examined the expression of 186 specific mRNAs in the pPVT of animals exposed to repeated swim stress (4 days of 15 min swim/day) with or without direct pPVT microinfusion of the orexin1 receptor antagonist SB334867 prior to each daily swim stress. Tissue was collected the next morning under basal non stressed conditions. Repeated stress and/or orexin receptor blockade significantly altered expression of only 9 specific genes including growth factors (Vegfa, Bax and Mt3), G-protein coupled receptors (Adora2a, Grm2 and Crhr1), immune-related genes (Ptgs2 and Cx3cr1) and an epigenetic-related gene (Hdac5). These genes represent potential targets for further characterization of orexin-mediated adaptations to repeated stress in the pPVT.

►Orexins act in paraventricular thalamus during repeated stress. ►Orexin actions regulate responses to subsequent novel stressors. ►Expression of 186 probable genes was examined using a custom PCR array. ►Expression of 3 genes was affected by blockade of orexin receptors and by stress. ►These are putative genes mediating orexin effects during repeated stress.