Document Detail


A new digitized method of the compulsive gnawing test revealed dopaminergic activity of salvinorin A in vivo.
MedLine Citation:
PMID:  20217638     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The compulsive gnawing (CG) test has been used for numerous years as an assay to determine the dopaminergic activity of various compounds. We developed a new method of quantification via a digitization step which allowed a more precise measurement of the gnawing activity. It was the aim of the present study to explore possible dopaminergic effects of salvinorin A (SA), the major active compound of Salvia divinorum, using the new digitized CG test. A group of experiments using male C57BL/6 mice were performed to validate the new method of quantification showing only significant increases of gnawing when the dopamine reuptake inhibitors buproprion (20 mg/kg, p. o.) and nomifensine (10 mg/kg, i. p.) were given concomitantly with apomorphine (10 mg/kg, i. p.). Different concentrations of the SA (1.0, 2.5, 5, and 10 mg/kg, i. p.) were tested with positive dopaminergic activity when administered with apomorphine which differed from the semisynthetic counterpart U-69593. Furthermore, the activity observed with SA was unsuccessfully antagonized by the κ-opioid receptor antagonist norbinaltorphimine (NorBNI; 10 and 20 mg/kg, i. p.), while the dopamine antagonist haloperidol did successfully block (0.06 mg/kg, i. p.) the gnawing activity seen with SA. Our data further strengthen the argument that salvinorin A is not a selective κ-opioid receptor agonist and is the first in vivo study that veers from salvinorin A acting solely like its synthetic counterparts. Furthermore, the digitized CG test system used in this study provides a new computational method to accurately detect behavior associated with dopaminergic neurotransmission.
Authors:
Stephen M Phipps; Veronika Butterweck
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Publication Detail:
Type:  Journal Article     Date:  2010-03-09
Journal Detail:
Title:  Planta medica     Volume:  76     ISSN:  1439-0221     ISO Abbreviation:  Planta Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0066751     Medline TA:  Planta Med     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1405-10     Citation Subset:  IM    
Copyright Information:
© Georg Thieme Verlag KG Stuttgart-New York.
Affiliation:
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610-0494, USA.
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