Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats.
Aashish S. Morani, Bronwyn Kivell, Thomas E. Prisinzano, Susan Schenk
Pharmacology, biochemistry, and behavior December 1, 2009 DOI: 10.1016/j.pbb.2009.09.002 via PubMed
Summary
AI-generated from the abstractPretreatment with several kappa-opioid receptor agonists, including salvinorin A (Sal A), the active compound in Salvia divinorum, reduced cocaine-induced drug-seeking in rats. After learning to self-administer cocaine, rats underwent extinction and then received a cocaine priming injection. Cocaine-induced reinstatement of drug-seeking was attenuated by U69593, U50488H, spiradoline, and Sal A. Sal A did not affect sucrose-reinforced responding or cocaine-induced hyperactivity, suggesting its effects are specific to drug-seeking. These findings indicate that Sal A, like other kappa-opioid agonists, can suppress cocaine-seeking behavior.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | U69593 U50488H spiradoline salvinorin A |
| Dose | U69593 0.3 mg/kg subcutaneous; U50488H 30.0 mg/kg intraperitoneal; spiradoline 1.0, 3.0 mg/kg intraperitoneal; salvinorin A 0.3, 1.0 mg/kg intraperitoneal; cocaine 20.0 mg/kg intraperitoneal |
| Duration | Single day |
| Citations | 91 |
| Key finding | Salvinorin A and other kappa-opioid receptor agonists attenuated cocaine-induced reinstatement of drug-seeking behavior in rats. |
Abstract
Our previous work indicated that pretreatment with the selective kappa-opioid receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of cocaine to reinstate extinguished cocaine-seeking behavior. The present study expanded these initial tests to include other traditional KOPr agonists, U50488H, spiradoline (SPR), and salvinorin A (Sal A), an active constituent of the plant Salvia divinorum. Following acquisition and stabilization of cocaine self-administration, cocaine-produced drug-seeking was measured. This test was conducted in a single day and comprised an initial phase of self-administration, followed by a phase of extinguished responding. The final phase examined reinstatement of extinguished cocaine self-administration followed by a priming injection of cocaine (20.0mg/kg, intraperitoneal (I.P.)) in combination with the various KOPr agonists. Cocaine-induced drug-seeking was attenuated by pretreatment with U69593 (0.3mg/kg, subcutaneous (S.C.)), U50488H (30.0mg/kg, I.P.), SPR (1.0, 3.0mg/kg, I.P.) and Sal A (0.3, 1.0mg/kg, I.P.). Sal A (0.3, 1.0mg/kg, I.P.) had no effect on operant responding to obtain sucrose reinforcement or on cocaine-induced hyperactivity. These findings show that Sal A, like other traditional KOPr agonists attenuates cocaine-induced drug-seeking behavior.