Abstract:
RATIONALE:Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. OBJECTIVES:This study represents a systematic examination of this hypothesis. METHODS:Salvinorin A was isolated from S. divinorum and was evaluated in a battery of in vitro and in vivo procedures designed to detect cannabinoid activity, including CB(1) receptor radioligand and [(35)S]GTPgammaS binding, calcium flux assay, in vivo cannabinoid screening tests, and drug discrimination. RESULTS:Salvinorin A did not bind to nor activate CB(1) receptors. In vivo salvinorin A produced pronounced hypolocomotion and antinociception (and to a lesser extent, hypothermia). These effects were blocked by the selective KOR antagonist, JDTic, but not by the CB(1) receptor antagonist rimonabant. Interestingly, however, rimonabant attenuated KOR activation stimulated by U69,593 in a [(35)S]GTPgammaS assay. Salvinorin A did not substitute for Delta(9)-tetrahydrocannabinol (THC) in mice trained to discriminate THC. CONCLUSIONS:These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvinorin A on the endocannabinoid system. Further, the results suggest that rimonabant reversal of salvinorin A effects in previous studies may be explained in part by rimonabant attenuation of KOR activation.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Walentiny DM,Vann RE,Warner JA,King LS,Seltzman HH,Navarro HA,Twine CE Jr,Thomas BF,Gilliam AF,Gilmour BP,Carroll FI,Wiley JLdoi
10.1007/s00213-010-1827-6subject
Has Abstractpub_date
2010-06-01 00:00:00pages
275-84issue
2eissn
0033-3158issn
1432-2072journal_volume
210pub_type
杂志文章abstract:RATIONALE:The development and validation of animal models of the cognitive impairments of schizophrenia have remained challenging subjects. OBJECTIVE:We review evidence from a series of experiments concerning an animal model that dissociates between the disruption of attentional capacities during acute illness periods...
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更新日期:2011-02-01 00:00:00
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更新日期:2010-03-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2015-05-01 00:00:00
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更新日期:2020-04-01 00:00:00
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更新日期:1988-01-01 00:00:00
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更新日期:2012-07-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-02-01 00:00:00