INHIBITORY INTERACTIONS BETWEEN ALPHA-2-ADRENERGIC AND OPOID BUT NOT NPY MECHANISMS CONTROLLING THE CRF-ACTH AXIS IN THE RAT

Following a series of investigations supporting the concept that the brain stem catecholaminergic (CA) system played a major stimulatory role on both basal and stress-triggered states of the hypothalamic-pituitary-adrenocortical (HPA) axis, across alpha-1 and beta-receptors and also via alpha-2 receptors [6, 11], the present study was designed to gain a deeper insight into the fine mechanism of functional interactions between the alpha-2 receptors mediated CA system and two peptidergic mechanisms, both shown to take part in the stimulatory control of the HPA axis: beta-endorphin and NPY. All experiments were conducted on rats whose noradrenergic bundles, which directly innervate the CRF neurons and are strongly implicated in the ether stress-induced corticotropic response [5], had been bilaterally obliterated by an intracerebral (i.c.) injection of 6-OHDA (NAB-X). Results showed that: (1) the blockade of the ether-stress induced ACTH response resulting from NAB-X was entirely reversed by an intraventricular (i.c.v.) infusion of the alpha-2 antagonist idazoxan (10 nmol), which appeared ineffective under basal conditions; (2) the restoration of a normal post-stress ACTH surge by i.c.v. idazoxan was itself blunted by, an i.c.v. pretreatment with naloxone (10 nmol), whereas an i.c. pretreatment with an anti-NPY serum appeared ineffective. These data suggest that, in addition to a stimulatory control exerted by postsynaptic alpha-2 receptors directly on CRF neurons, other alpha-2 receptors participate, exclusively under the stress conditions above, in a tonic inhibitory control, indirectly mediated to the HPA axis across a stimulatory opioid, but not NPY regulatory component.