Endocrinology, Vol 135, 2549-2557, Copyright © 1994 by Endocrine Society

ARTICLES

Blockade of alpha 2-adrenoceptors stimulates basal and stress-induced adrenocorticotropin secretion in the developing rat through a central mechanism independent from corticotropin-releasing factor and arginine vasopressin

M Grino, O Paulmyer-Lacroix, M Faudon, M Renard and G Anglade
Laboratoire de Neuroendocrinologie Experimentale, INSERM U-297, Institut Federatif Jean Roche, Marseille, France.

In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly reduced during the first 2 weeks of life [stress-hyporesponsive period (SHRP)]. In this report, we studied the effect of idazoxan (an alpha 2-adrenergic antagonist) on plasma ACTH and corticosterone levels in 8-day-old rats. Indeed, it is known that in the adult rat, blockade of alpha 2-adrenoceptors increases ACTH secretion stimulated by CRF and arginine vasopressin (AVP) injection. Injection of 2.5 micrograms/g idazoxan induced a rapid (within 30 min) increase in basal plasma ACTH and corticosterone levels that lasted for 60 min. Injection of increasing doses of idazoxan led to a dose-dependent stimulation of ACTH and corticosterone levels. Administration of 2.5 micrograms/g idazoxan significantly increased the ACTH response to insulin-induced hypoglycemia, whereas it potentiated and accelerated the ACTH response to ether exposure stress. We next examined ACTH secretion from superfused anterior pituitary glands. Neither the alpha 2-adrenergic agonist clonidine nor idazoxan changed the basal ACTH secretory rate. Idazoxan had no effect on CRF- and AVP- stimulated ACTH secretion. This indicates that in vivo, idazoxan acts at a suprapituitary level. To investigate a possible effect of idazoxan on presynaptic alpha 2-adrenoceptors, we studied the effect of idazoxan on the concentrations of norepinephrine (NE) and L-DOPA in punches of locus coeruleus after dopa-decarboxylase blockade. Idazoxan injection induced a decrease in the NE content, without changing L-DOPA levels, indicating that idazoxan can act at the level of presynaptic alpha 2- adrenoceptors, inducing an increased release and/or degradation of NE without any effect on catecholamines synthesis. Finally, we investigated a possible involvement of CRF and AVP in mediating the effect of alpha 2-adrenoceptor blockade on ACTH secretion. Passive immunization against CRF or AVP did not change the ACTH response to idazoxan administration, whereas idazoxan pretreatment had simply an additive effect on CRF- and lysine vasopressin-stimulated ACTH secretion. In conclusion, our data demonstrate that during the SHRP, blockade of alpha 2-adrenoceptors induces an increase in both basal and stress-induced ACTH secretion. They suggest that a decreased catecholaminergic tone, consecutive to an increased occupation of alpha 2-adrenoceptors, acting through a central mechanism independent from CRF and AVP may be responsible for the SHRP in the developing rat.

This article has been cited by other articles:

				C. J. Rice, C. A. Sandman, M. R. Lenjavi, and T. Z. Baram A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress Endocrinology, October 1, 2008; 149(10): 4892 - 4900. [Abstract] [Full Text] [PDF]

				S. Moriceau, D. A. Wilson, S. Levine, and R. M. Sullivan Dual circuitry for odor-shock conditioning during infancy: corticosterone switches between fear and attraction via amygdala. J. Neurosci., June 21, 2006; 26(25): 6737 - 6748. [Abstract] [Full Text] [PDF]

				A. Varma, J. He, B.-C. Shin, L. A. Weissfeld, and S. U. Devaskar Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1132 - E1141. [Abstract] [Full Text] [PDF]

				D. P. Finn, A. L. Hudson, H. Kinoshita, T. L. Coventry, D. S. Jessop, D. J. Nutt, and M. S. Harbuz Imidazoline2 (I2) Receptor- and {alpha}2- Adrenoceptor-Mediated Modulation of Hypothalamic-Pituitary-Adrenal Axis Activity in Control and Acute Restraint Stressed Rats J Psychopharmacol, March 1, 2004; 18(1): 47 - 53. [Abstract] [PDF]

				A. Varma, J. He, L. Weissfeld, and S. U. Devaskar Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1560 - R1566. [Abstract] [Full Text] [PDF]