title: Changes in catecholaminergic pathways innervating paraventricular nucleus and pituitary-adrenal axis response during morphine dependence: implication of alpha(1)- and alpha(2)-adrenoceptors.
abstract: 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 alpha(1)- or alpha(2)-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 alpha(1)- and alpha(2)-adrenoceptor activation. Activation of dopaminergic pathways might not contribute to the neuroendocrine response during withdrawal.
authors.affiliation: Department of Physiology and Pharmacology, Unit of Pharmacology, University School of Medicine, Murcia, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Laorden
authors.forename: G
authors.initials: G
authors.lastname: Fuertes
authors.forename: A
authors.initials: A
authors.lastname: González-Cuello
authors.forename: M V
authors.initials: MV
authors.lastname: Milanés
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D009292:Narcotic Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D009270:Naloxone; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine; D011224:Prazosin