TY - JOUR
T1 - A single injection of a novel kappa opioid receptor agonist salvinorin A attenuates the expression of cocaine-induced behavioral sensitization in rats
AU - Morani, Aashish S.
AU - Schenk, Susan
AU - Prisinzano, Thomas E.
AU - Kivell, Bronwyn Maree
PY - 2012/4
Y1 - 2012/4
N2 - Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side-effects such as sedation, dysphoria, and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaine-induced drug seeking in a model of relapse in rats. The present study evaluated the effects of acute Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment with a dose of Sal A that decreased drug seeking in a previous study (0.3 mg/kg) significantly attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution. However, Sal A decreased climbing and swimming time and increased time spent immobile in the forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned aversion, suggesting improved potential compliance. However, prodepressive effects were also produced and these effects may limit the therapeutic potential.
AB - Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side-effects such as sedation, dysphoria, and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaine-induced drug seeking in a model of relapse in rats. The present study evaluated the effects of acute Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment with a dose of Sal A that decreased drug seeking in a previous study (0.3 mg/kg) significantly attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution. However, Sal A decreased climbing and swimming time and increased time spent immobile in the forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned aversion, suggesting improved potential compliance. However, prodepressive effects were also produced and these effects may limit the therapeutic potential.
KW - behavioral sensitization
KW - conditioned taste aversion
KW - depression
KW - forced swim test
KW - kappa opioid agonist
KW - rat
KW - salvinorin A
UR - http://www.scopus.com/inward/record.url?scp=84858702496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858702496&partnerID=8YFLogxK
U2 - 10.1097/FBP.0b013e3283512c1e
DO - 10.1097/FBP.0b013e3283512c1e
M3 - Article
C2 - 22293826
AN - SCOPUS:84858702496
SN - 0955-8810
VL - 23
SP - 162
EP - 170
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 2
ER -