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A single injection of a novel κ opioid receptor agonist salvinorin A attenuates the expression of cocaine-induced behavioral sensitization in rats.

Aashish S Morani, Susan Schenk, Thomas E Prisinzano, Bronwyn Maree Kivell

Behavioural Pharmacology April 2012 DOI: 10.1097/fbp.0b013e3283512c1e (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study in rats Peer reviewed
Population Rats
Interventions Salvinorin A cocaine
Dose 0.3 mg/kg
Measures forced swim test, conditioned taste aversion, spontaneous locomotion, cocaine sensitization
Topics Salvia divinorum
Key findings Salvinorin A at 0.3 mg/kg attenuated the expression of cocaine sensitization in rats without affecting spontaneous locomotion or producing conditioned taste aversion, unlike traditional kappa opioid agonists. However, it decreased climbing and swimming and increased immobility in the forced swim test, indicating prodepressive effects that the authors suggest may limit its therapeutic potential.

Abstract

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.

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