RT Journal Article
SR Electronic
T1 Changes in Catecholaminergic Pathways Innervating Paraventricular Nucleus and Pituitary-Adrenal Axis Response during Morphine Dependence: Implication of α<sub>1</sub>- and α<sub>2</sub>-Adrenoceptors
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 578
OP 584
VO 293
IS 2
A1 Maria Luisa Laorden
A1 Gregorio Fuertes
A1 Ana González-Cuello
A1 Maria Victoria Milanés
YR 2000
UL http://jpet.aspetjournals.org/content/293/2/578.abstract
AB We have previously shown an enhanced activity of the pituitary-adrenal response in rats dependent on morphine, which occurs concomitantly with an increase in the activity of catecholaminergic terminals in the hypothalamic paraventricular nucleus (PVN). The present study examined the possible role of noradrenergic system in the regulation of opioid withdrawal-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis activity. Rats were given morphine by s.c. implantation of morphine pellets for 7 days. On the seventh day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), rats were sacrificed 30 min later, and changes in noradrenaline (NA) turnover (estimated by the 3-methoxy-4-hydroxyphenylethylen glycol/NA ratio) and in dopamine turnover (estimated by the 3,4-dihydroxyphenylacetic acid/dopamine ratio) in the PVN (HPLC with electrochemical detection) and in plasma corticosterone levels were determined. We found a parallelism between the behavioral signs of withdrawal, an increased activity of noradrenergic and dopaminergic terminals in the PVN, and the hypersecretion of the HPA axis. Pretreatment with α1- or α2-adrenoceptor antagonists prazosin or yohimbine, respectively, 15 min before naloxone administration significantly prevented the withdrawal-induced corticosterone hypersecretion and attenuated the behavioral signs of morphine withdrawal. In addition, biochemical analysis indicated that both prazosin and yohimbine completely abolished the withdrawal-induced increase in NA turnover in the PVN. In contrast, neither prazosin nor yohimbine modified the hyperactivity of dopaminergic terminals in the PVN during withdrawal. Collectively, these data suggest that the secretory activity in the HPA axis after morphine withdrawal results from an increase in noradrenergic activity that is dependent on α1- and α2-adrenoceptor activation. Activation of dopaminergic pathways might not contribute to the neuroendocrine response during withdrawal. The American Society for Pharmacology and Experimental Therapeutics