Elevated glucocorticoid levels are responsible for induction of tyrosine hydroxylase mRNA expression, phosphorylation, and enzyme activity in the nucleus of the solitary tract during morphine withdrawal

Cristina Núñez, Anna Földes, Domingo Pérez-Flores, J. Carlos García-Borrón, M. Luisa Laorden, Krisztina J. Kovács, M. Victoria Milanés

Research output: Contribution to journalArticle

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Abstract

Chronic opiate exposure induces neurochemical adaptations in the noradrenergic system. Enhanced responsiveness of the hypothalamo-pituitary- adrenal axis after morphine withdrawal has been associated with hyperactivity of ascending noradrenergic input from the nucleus of the solitary tract (NTS-A2) cell group to the hypothalamic paraventricular nucleus (PVN). This study addressed the role of morphine withdrawal-induced corticosterone (CORT) release in regulation of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis in adrenalectomized (ADX) rats supplemented with low CORT pellet (ADX plus CORT). Present results show that in sham-ADX rats, noradrenergic neurons in the NTS-A2 became activated during morphine withdrawal, as indicated by increased THmRNA expression. However, this induction of TH expression is not detected in ADX plus CORT rats that are unable to mount CORT secretory response to morphine withdrawal. Total TH protein levels were elevated in the NTS-A2 from sham-operated rats during morphine dependence and withdrawal, whereas we did not find any alteration in ADX plus CORT animals. Furthermore, high levels of TH phosphorylated (activated) at Ser31 (but not at Ser40) were found in the A 2 area from sham-morphine withdrawn rats. Consistent with these effects, we observed an increase in the enzyme activity of TH in the PVN. However, induction of morphine withdrawal to ADX plus CORT animals did not alter the phosphorylation (activation) of TH in NTS-A2 and decreased TH activity in the PVN. These results suggest the existence of a positive reverberating circle in which elevated glucocorticoids during morphine abstinence play a permissive role in morphine withdrawalinduced activation of noradrenergic pathway innervating the PVN.

Original languageEnglish
Pages (from-to)3118-3127
Number of pages10
JournalEndocrinology
Volume150
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Solitary Nucleus
Tyrosine 3-Monooxygenase
Morphine
Glucocorticoids
Corticosterone
Phosphorylation
Messenger RNA
varespladib methyl
Paraventricular Hypothalamic Nucleus
Enzymes
Opiate Alkaloids
Morphine Dependence
Adrenergic Neurons
Catecholamines

ASJC Scopus subject areas

  • Endocrinology

Cite this

Elevated glucocorticoid levels are responsible for induction of tyrosine hydroxylase mRNA expression, phosphorylation, and enzyme activity in the nucleus of the solitary tract during morphine withdrawal. / Núñez, Cristina; Földes, Anna; Pérez-Flores, Domingo; García-Borrón, J. Carlos; Laorden, M. Luisa; Kovács, Krisztina J.; Milanés, M. Victoria.

In: Endocrinology, Vol. 150, No. 7, 07.2009, p. 3118-3127.

Research output: Contribution to journalArticle

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