Effects of mesyl salvinorin B alone and in combination with naltrexone on alcohol deprivation effect in male and female mice.
Yan Zhou, Rachel S Crowley, Thomas E Prisinzano, Mary Jeanne Kreek
Neuroscience Letters April 23, 2018 DOI: 10.1016/j.neulet.2018.02.056 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female mice |
| Interventions | Mesyl Salvinorin B Naltrexone |
| Dose | 0.3-3 mg/kg MSB; 1 mg/kg naltrexone |
| Duration | 3-week intermittent access alcohol drinking, 1-week abstinence, then acute administration |
| Topics | Salvia divinorum |
| Keywords | Alcohol deprivation effect Combined therapy Kop-r Mesyl salvinorin b Naltrexone Relapse |
| Key findings | MSB at 3 mg/kg prevented the alcohol deprivation effect, and a combination of MSB (0.3 mg/kg) with naltrexone (1 mg/kg) also reduced it at lower individual doses. |
Abstract
Alcohol relapse plays a major role in alcohol dependence and is an important focus for the treatment of alcoholism. The alcohol deprivation effect (ADE) is a widely used paradigm in rodents to model the relapse episodes that occur in human alcoholics. Mesyl Salvinorin B (MSB) is a potent and selective kappa opioid receptor (KOP-r) full agonist, with fewer side effects (e.g., sedation or anhedonia) than classic KOP-r full agonists and a longer duration of action in mice than the structurally similar salvinorin A. We have recently found that MSB prevents cocaine seeking in a rat self-administration model and reduces excessive alcohol drinking in a mouse escalation model via a KOP-r-mediated mechanism. Here, we further investigated whether MSB alone (0.3-3 mg/kg) or in combination with naltrexone (mu-opioid receptor antagonist at 1 mg/kg) altered alcohol "relapse" drinking using a mouse ADE paradigm. Both male and female mice, exposed to 3-week intermittent access alcohol drinking in a two-bottle choice paradigm with 24-h access every other day, developed excessive alcohol intake and then displayed pronounced ADE after 1-week abstinence. Acute administration of MSB prevented the ADE at 3 mg/kg in both male and female mice. Upon investigation of potential synergistic effects between naltrexone and MSB, we found that acute administration of a combination of MSB (0.3 mg/kg) and naltrexone (1 mg/kg) reduced the ADE at doses lower than those individual effective doses, with no sex difference. Our study suggests that the KOP-r full agonist MSB both alone and in combination with naltrexone shows potential in alcohol "relapse" treatment models.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 2
Cites 4
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- Pharmacology and anti-addiction effects of the novel κ opioid receptor agonist Mesyl Sal B, a potent and long-acting analogue of salvinorin A. British Journal of Pharmacology 2015
- Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands. Journal of Medicinal Chemistry July 28, 2005