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, 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, 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.
Gaillet
S
S
Endocrinological Neurobiology Laboratory, URA 1197 CNRS, University of Montpellier-2, France.
Malaval
F
F
Barbanel
G
G
Pelletier
G
G
Assenmacher
I
I
Szafarczyk
A
A
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019329:Idazoxan; D007276:Injections, Intraventricular; D009270:Naloxone / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D013312:Stress, Physiological; D001615:beta-Endorphin / Q000378:metabolism / Q000494:pharmacology
D004146:Dioxanes; D006728:Hormones; D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D011957:Receptors, Opioid; D009270:Naloxone; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D019329:Idazoxan