Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats.
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.
Morani
Aashish S
AS
School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand. aashish.morani@vuw.ac.nz
Kivell
Bronwyn
B
Prisinzano
Thomas E
TE
Schenk
Susan
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control / Q000523:psychology; D044482:Benzeneacetamides / Q000494:pharmacology / Q000627:therapeutic use*; D003042:Cocaine / Q000008:administration & dosage*; D045785:Diterpenes, Clerodane / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D012646:Self Administration
D044482:Benzeneacetamides; D045785:Diterpenes, Clerodane; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003042:Cocaine; C045444:U 69593; C051272:spiradoline; C090499:salvinorin A