Paradoxical reinforcing properties of apomorphine: Effects of nucleus accumbens and area postrema lesions

Abstract

Apomorphine (0.01–10.0 mg/kg, subcutaneously) paradoxically produced both dose-dependent aversive and positive reinforcing effects, as measured in conditioned taste aversion and place preference paradigms, respectively. The conditioned taste aversions produced by apomorphine were not modified in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens (producing 92% depletion of dopamine in the nucleus accumbens) nor in rats with thermal lesions of the area postrema. Both types of lesions were behaviorally verified as effective in other paradigms; the 6-OHDA lesions potentiated the facilitatory effects of apomorphine on locomotor activity in photocell cages, and the area postrema lesions attenuated the conditioned taste aversions to a novel flavor paired with scopolamine methylnitrate (1.0 mg/kg, intraperitoneally). However, 6-OHDA lesions of the nucleus accumbens did clearly potentiate the conditioned place preferences induced by apomorphine. These results suggest that both the positive reinforcing and locomotor effects of apomorphine may partially result from activation of post-synaptic dopamine receptors in the nucleus accumbens. Moreover, the dissociation of apomorphine's aversive and positive reinforcing properties revealed by the 6-OHDA lesions may provide the first step in attempts to pinpoint the different brain sites of action where apomorphine produces its opposite motivational effects.