Central corticotropin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress

The role of brain corticotropin-releasing hormone receptors in modulating h ypothalamic-pituitary-adrenal and sympathoadrenal responses to acute immobi lization stress was studied in conscious rats under central corticotropin-r eleasing hormone receptor blockade by intracerebroventicular injection of a peptide corticotropin-releasing hormone receptor antagonist. Blood for cat echolamines, adrenocorticotropic hormone and corticosterone levels was coll ected through vascular catheters, and brains were removed at 3 h for in sit u hybridization for tyrosine hydroxylase messenger RNA in the locus coerule us, and corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA in the hypothalamic paraventricular nucleus. Centra l corticotropin-releasing hormone receptor blockade reduced the early incre ases in plasma epinephrine and dopamine, but not norepinephrine, during str ess. Immobilization stress increased tyrosine hydroxylase messenger RNA lev els in the locus coeruleus by 36% in controls, but not in corticotropin-rel easing hormone antagonist-injected rats. In control rats, corticotropin-rel easing hormone messenger RNA and type 1 corticotropin-releasing hormone rec eptor messenger RNA in the paraventricular nucleus increased after stress ( P < 0.01), and these responses were attenuated by central corticotropin-rel easing hormone receptor blockade. In contrast, central corticotropin-releas ing hormone antagonist potentiated plasma adrenocorticotropic hormone respo nses, but slightly attenuated plasma corticosterone responses to stress. The inhibition of plasma catecholamine and locus coeruleus tyrosine hydroxy lase messenger RNA responses to stress by central corticotropin-releasing h ormone receptor blockade supports the notion that central corticotropin-rel easing hormone regulates sympathoadrenal responses during stress. The atten uation of stress-induced corticotropin-releasing hormone and corticotropin- releasing hormone receptor messenger RNA responses by central corticotropin -releasing hormone receptor blockade suggests direct or indirect positive f eedback effects of corticotropin-releasing hormone receptor ligands on cort icotropin-releasing hormone expression, whereas additional mechanisms poten tiate adrenocorticotropic hormone responses at the pituitary level. In addi tion, changes in neural activity by central corticotropin-releasing hormone are likely to modulate adrenocortical responsiveness during stress. Publis hed by Elsevier Science Ltd.