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Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine.
- Source :
-
Scientific reports [Sci Rep] 2020 Dec 04; Vol. 10 (1), pp. 21275. Date of Electronic Publication: 2020 Dec 04. - Publication Year :
- 2020
-
Abstract
- Severe withdrawal symptoms triggered by cessation of long-term opioid use deter many individuals from seeking treatment. Opioid substitution and α2-adrenergic agonists are the current standard of pharmacotherapy for opioid use disorder in western medicine; however, each is associated with significant complications. Heantos-4 is a non-opioid botanical formulation used to facilitate opioid detoxification in Vietnam. While ongoing clinical use continues to validate its safety and effectiveness, a mechanism of action accounting for these promising effects remains to be specified. Here, we assess the effects of Heantos-4 in a rat model of morphine-dependence and present evidence that alleviation of naloxone-precipitated somatic withdrawal signs is related to an upregulation of mesolimbic dopamine activity and a consequent reversal of a hypodopaminergic state in the nucleus accumbens, a brain region implicated in opioid withdrawal. A central dopaminergic mechanism is further supported by the identification of l-tetrahydropalmatine as a key active ingredient in Heantos-4, which crosses the blood-brain barrier and shows a therapeutic efficacy comparable to its parent formulation in attenuating withdrawal signs. The anti-hypodopaminergic effects of l-tetrahydropalmatine may be related to antagonism of the dopamine autoreceptor, thus constituting a plausible mechanism contributing to the effectiveness of Heantos-4 in facilitating opioid detoxification.
- Subjects :
- Analgesics, Opioid adverse effects
Animals
Berberine Alkaloids metabolism
Berberine Alkaloids pharmacology
Dopamine metabolism
Dopamine Antagonists metabolism
Dopamine Antagonists pharmacology
Drug Evaluation, Preclinical
Male
Morphine adverse effects
Nucleus Accumbens metabolism
Phytotherapy
Plant Extracts metabolism
Plant Extracts pharmacology
Quinpirole
Rats, Sprague-Dawley
Berberine Alkaloids therapeutic use
Dopamine Antagonists therapeutic use
Nucleus Accumbens drug effects
Plant Extracts therapeutic use
Substance Withdrawal Syndrome drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33277581
- Full Text :
- https://doi.org/10.1038/s41598-020-78083-x