Selective antagonist at D3 receptors, but not non-selective partial agonists, influences the expression of cocaine-induced conditioned place preference in free-feeding rats

The non-selective dopamine (DA) D3 partial agonist BP 897 influenced rats' seeking behavior induced by cocaine-associated cues but there are contradictions about its ability to modulate cocaine-induced conditioned place preference (CPP), and mechanisms involved. We therefore re-evaluated its activity on both acquisition and expression of these behaviors, taking into consideration the actual brain concentrations of unchanged drug and its potential active metabolite 1-(2-methoxyphenyl)-piperazine (oOCH3PP), as well as its negative motivational properties. BP 897 induced conditioned place aversion (CPA) at 3 mg/kg, but not at 0.3 and 1 mg/kg. However, in this range of amply spaced doses BP 897 did not affect the acquisition and expression of cocaine (10 mg/kg i.p.) CPP in rats, although its brain concentrations were well above those affecting in vitro D3 receptors. Concentrations of oOCH3PP were below the limits of quantification of the analytical procedure. As concerns the expression behavior, its structurally and pharmacologically related derivative N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]furan-2-carboxamide (1 and 3 mg/kg, i.p.) also had no such effect. By contrast, the selective D3 receptor antagonist SB-277011-A (3 mg/kg, i.p.) antagonized the expression of cocaine-induced CPP, supporting the suggestion that “full” antagonist activity at D3 receptors is necessary to prevent 10 mg/kg cocaine-induced place conditioning in free-feeding rats.