Abstract:
:Somatic and motivational symptoms accompanying opiate withdrawal are considered one of the major reasons for relapse to opiate-seeking and opiate-taking behaviors. These symptoms are accompanied by the activation of stress-related processes including hypothalamic-pituitary-adrenal axis activity and noradrenergic (NA) signaling. In particular, the NA system plays an important role in the expression of somatic signs of opiate withdrawal, whereas glucocorticoid (GR) and mineralocorticoid receptors (MR) are activated during opiate abstinence. The purpose of our study was to examine the roles of α1-, α2-, and β-adrenoceptors (ARs) as well as GR and MR, in the formation and expression of physiological and motivational symptoms of morphine withdrawal. We showed that systemic pretreatment with the selective α1-AR antagonist prazosin (0-1 mg/kg), the selective α2-AR antagonist RX821002 (0-2 mg/kg), the selective β-adrenergic antagonist, propranolol (0-10 mg/kg), or the selective MR antagonist spironolactone (0-50 mg/kg), but not the selective GR antagonist mifepristone (0-40 mg/kg), decreased somatic symptoms of naloxone-precipitated morphine withdrawal in mice chronically treated with morphine. In contrast, only propranolol pretreatment attenuated the dysphoric affective state accompanying naloxone-precipitated morphine withdrawal as assessed in the conditioned place aversion (N-CPA) paradigm. Together, our results demonstrate the important roles of noradrenergic receptors in the modulation of somatic, but not motivational/affective, symptoms of morphine withdrawal. In addition MR but not GR regulates the expression of only somatic symptoms of morphine withdrawal.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Solecki WB,Kus N,Gralec K,Klasa A,Pradel K,Przewłocki Rdoi
10.1016/j.bbr.2018.11.041subject
Has Abstractpub_date
2019-03-15 00:00:00pages
146-157eissn
0166-4328issn
1872-7549pii
S0166-4328(18)30597-7journal_volume
360pub_type
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