Abstract：
AIMS:Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model. METHODS:Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20-30 min following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 h after the last dose of carisoprodol. RESULTS:The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75-100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24h following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15-30 min of administration. CONCLUSIONS:Carisoprodol treatment resulted in tolerance and antagonist-precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds.
journal_name
Drug Alcohol Dependjournal_title
Drug and alcohol dependenceauthors
Gatch MB,Nguyen JD,Carbonaro T,Forster MJdoi
10.1016/j.drugalcdep.2011.10.010subject
Has Abstractpub_date
2012-06-01 00:00:00pages
29-34issue
1-3eissn
0376-8716issn
1879-0046pii
S0376-8716(11)00446-7journal_volume
123pub_type
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pub_type： 临床试验,杂志文章,随机对照试验
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