Spironolactone decreases the somatic signs of opiate withdrawal by blocking the mineralocorticoid receptors (MR)

Autor: M. Victoria Milanés, M. Luisa Laorden, Javier Navarro-Zaragoza
Rok vydání: 2014
Předmět:
Male
Hypothalamo-Hypophyseal System
medicine.medical_specialty
Tyrosine 3-Monooxygenase
medicine.drug_class
Narcotic Antagonists
Hypothalamus
Pituitary-Adrenal System
(+)-Naloxone
Spironolactone
Toxicology
Rats
Sprague-Dawley
Norepinephrine
chemistry.chemical_compound
Glucocorticoid receptor
Mineralocorticoid receptor
Internal medicine
Animals
Medicine
Phosphorylation
Mineralocorticoid Receptor Antagonists
Morphine
Naloxone
business.industry
Kindling
Antagonist
Opioid-Related Disorders
Substance Withdrawal Syndrome
Analgesics
Opioid
Enzyme Activation
Disease Models
Animal
Receptors
Mineralocorticoid
Endocrinology
chemistry
Mineralocorticoid
business
Proto-Oncogene Proteins c-fos
hormones
hormone substitutes
and hormone antagonists
Paraventricular Hypothalamic Nucleus
Signal Transduction
medicine.drug
Zdroj: Toxicology. 326:36-43
ISSN: 0300-483X
DOI: 10.1016/j.tox.2014.10.002
Popis: Pharmacological evidence has accumulated showing that glucocorticoids and glucocorticoid receptor (GR) facilitate several responses to different drugs of abuse. Recent findings have attributed a prominent role to the mineralocorticoid receptor (MR) in modulating behavior during the addictive process. The purpose of this study was to investigate the effects of MR blockade on: brain stress system responses to naloxone-induced morphine withdrawal, the somatic signs of abstinence; the effects of morphine withdrawal on noradrenaline (NA) turnover in the paraventricular nucleus (PVN), c-Fos expression and tyrosine hydroxylase (TH) phosphorylated at Ser31 levels in the nucleus tractus solitarius noradrenergic cell group (NTS-A2); and finally, hypothalamus-pituitary-adrenocortical (HPA) axis activity. The role of MR signaling was assessed with i.p. pretreatment with the MR antagonist, spironolactone. Rats were implanted with two morphine (or placebo) pellets. Six days later rats were pretreated with spironolactone or vehicle 30min before naloxone. The physical signs of abstinence, NA turnover, TH activation, c-Fos expression and the HPA axis activity were measured using HPLC, immunoblotting and RIA. Spironolactone attenuated the somatic signs of withdrawal that were seen after naloxone administration to chronic morphine treated animals. On the other hand, pretreatment with spironolactone resulted in no significant modification of the increased NA turnover, TH activation, c-Fos expression or HPA axis activity that occurred during morphine withdrawal. These results suggest that somatic signs of opiate withdrawal are modulated by MR signaling. However, blockade of MR did not significantly alter the brain stress system response to morphine withdrawal.
Databáze: OpenAIRE
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