The acute administration of the selective dopamine D₃ receptor antagonist SB‐277011A reverses conditioned place aversion produced by naloxone precipitated withdrawal from acute morphine administration in rats

Abstract

We examined the effect of SB-277011A, a selective D3 receptor antagonist, on the conditioned place aversion (CPA) response associated with naloxone-induced withdrawal from acute morphine administration in male Sprague-Dawley rats. Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg i.p.) and prior to placing the animals in one specific chamber of the test apparatus. All animals were subjected to 2 of these trials. A significant CPA occurred in animals that received an i.p. injection of vehicle 30 minutes prior to the measurement of chamber preference. The pretreatment of animals (30 minutes prior to testing) with 3 mg/kg i.p. of SB-277011A did not significantly alter the CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg i.p. of SB-277011A significantly decreased the CPA compared to vehicle-treated animals. In fact, the 12 and 24 mg/kg doses of SB-277011A significantly increased the time spent in the chamber where animals were paired with morphine and naloxone. These results suggest that the selective antagonism of D3 receptors attenuates the CPA produced by a model of naloxone-induced withdrawal from acute morphine dependence.

The selective D3receptor antagonist SB-277011A attenuates morphine-triggered reactivation of expression of cocaine-induced conditioned place preference

“…The present finding that selective D 3 receptor antagonism blocks relapse to cocaine‐seeking behavior in the reactivation model is congruent with our previous findings that—in the reinstatement model of relapse—selective D 3 receptor antagonism blocks relapse to drug‐seeking behavior triggered by cocaine (Peng et al, ; Vorel et al, ; Xi et al, ), methamphetamine (Higley et al, ), nicotine (Andreoli et al, ), stress (Xi et al, ), cocaine‐associated environmental cues (Gilbert et al, ), methamphetamine‐associated environmental cues (Higley et al, ), and ethanol plus ethanol‐associated environmental cues (Heidbreder et al, ) (for reviews, see Gardner, ; Heidbreder and Newman, ; Heidbreder et al, ; Xi and Gardner, ). The present findings are also conceptually congruent with our recent finding that selective dopamine D 3 receptor antagonism reverses the conditioned place aversion produced by naloxone‐precipitated morphine withdrawal in rats (Rice et al, ).…”

The selective dopamine D3 receptor antagonist SB‐277011A attenuates drug‐ or food‐deprivation reactivation of expression of conditioned place preference for cocaine in male sprague‐dawley rats

“…For example, SB‐277011A (6, 12, or 24 mg kg −1 i.p.) significantly decreases the conditioned place aversion produced by naloxone‐precipitated morphine withdrawal in rats (Rice et al, ). SB‐277011A also dose‐dependently blocks the expression of conditioned fear in rats produced by stimulus‐shock pairings (Swain et al, 2008).…”

Dopamine D3Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs

“…Whereas the potential hypertensive effect of a dopamine D 3 receptor antagonist may preclude using this approach to treat stimulant use disorders, it may not preclude treating other substance use disorders such as nicotine (Mugnaini et al, 2013), alcohol (te Beek et al, 2012, and opiates (Ashby et al, 2003;Rice et al, 2012). Because of the chronic and relapsing nature of substance abuse, any therapy would likely be repetitive and prolonged.…”