Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY
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Salvinorin A is a potent naturally occurring, nonnitrogenous, kappa-opioid selective agonist (Roth et al., PNAS, 99: 11934-11939, 2002). Synthetic kappa-opioid agonists have been found to decrease dopamine levels in the nucleus accumbens and caudate putamen in rodents. Thus, effects of salvinorin A on basal dopamine levels in the caudate putamen were studied. Methods: Male C57BL/6J mice (8 weeks old) were allowed to acclimate for 1 week before surgery. A CMA guide cannula was implanted into the caudate putamen. After 4 days recovery, a dialysis probe was lowered into the caudate putamen and the mouse was placed in an individual microdialysis chamber. The next morning, experiments were carried out on freely moving animals. After collection of baseline samples, salvinorin A was administered i.p. (0, 0.32, 1 and 3.2 mg/kg). Dialysates were collected in 20-min samples, for 3 hrs. Results: ANOVA showed that salvinorin A decreased dopamine levels in a dose dependent manner (p < 0.05). The significant decrease in dopamine levels produced by the highest dose of salvinorin A (3.2 mg/kg) was completely blocked by pre-injection with 10 mg/kg of the kappa-antagonist nor-BNI. Conclusion: In the caudate putamen, the naturally occurring compound, salvinorin A, reduces dopamine levels through kappa-opioid receptors. Support: NIH-NIDA P60 DA05130 and KO5 DA00049 to MJK.