Effect of naloxone on central adrenergic stimulation of corticosterone secretion

The interaction of central opioid with adrenergic system in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in conscious rats. All the tested drugs were administered intracerebroventricularly (i.c.v.), naloxone 15 min before the adrenergic agonists. Phenylephrine (30 micrograms), clonidine (10 micrograms) and isoprenaline (10 micrograms), the alpha 1-, alpha 2- and beta-adrenergic agonists as well as noradrenaline (10 micrograms) and adrenaline (10 micrograms) significantly increased the serum corticosterone levels, measured 1 h after drug administration. Naloxone (0.01-1 microgram) did not markedly influence the corticosterone response to phenylephrine and isoprenaline and diminished by a half the response to clonidine. Naloxone also significantly decreased the corticosterone response to noradrenaline but did not substantially alter the response to adrenaline. Noradrenaline potently stimulates the HPA axis via alpha 2-adrenoceptors, whereas adrenaline involves mainly alpha 1- and beta-adrenergic receptors. These results indicate that central opioid system is significantly involved in mediating the pituitary-adrenocortical response to clonidine and noradrenaline but not phenylephrine, isoprenaline and adrenaline. This suggests an interaction of opioids at central alpha 2- but not alpha 1-receptor sites.