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.
BACKGROUND
Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective kappa opioid receptor agonist in vitro. It has been shown that kappa agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents.


OBJECTIVE
To study the effects of salvinorin A on basal dopamine levels in the caudate putamen and nucleus accumbens, and to determine whether salvinorin A induces conditioned place preference or aversion and changes in locomotor activity in the mouse.


METHODS
In the first experiment, changes in dopamine levels in these brain regions after administration of salvinorin A were measured with in vivo microdialysis. In the second experiment, we examined whether salvinorin A led to conditioned place preference or aversion, and changes in locomotor activity during conditioning sessions.


RESULTS
The higher doses of salvinorin A studied (1.0 mg/kg and 3.2 mg/kg, i.p.) significantly decreased dopamine levels in the caudate putamen, but not in the nucleus accumbens, and this effect was completely blocked by pre-injection with 10 mg/kg of the kappa opioid receptor antagonist nor-binaltorphimine. The same doses of salvinorin A caused conditioned place aversion and decreased locomotor activity.


CONCLUSIONS
The inhibitory effect of salvinorin A on striatal dopamine levels may contribute to its induction of conditioned place aversion and decreases in locomotion in mice. These findings are consistent with the in vitro characterization of salvinorin A as a kappa opioid receptor agonist. It is of interest that a compound such as salvinorin A, that lowers striatal dopamine levels and leads to conditioned place aversion in rodents, is self-administered by humans under certain conditions.
Zhang
Yong
Y
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, Box 171 New York, NY 10021, USA. zhangyo@mail.rockefeller.edu
Butelman
Eduardo R
ER
Schlussman
Stefan D
SD
Ho
Ann
A
Kreek
Mary Jeanne
MJ
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D027544:Salvia
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D010936:Plant Extracts; D017473:Receptors, Opioid, kappa; C090499:salvinorin A; D004298:Dopamine