NMDA-induced lesions of the nucleus accumbens core increase the innately rewarding saccharin solution intake and methamphetamine-induced conditioned place preference but not conditioned taste aversion in rats.

The role of the nucleus accumbens (NAc) core in determining the valence of innately rewarding saccharin solution intake, methamphetamine (MAMPH)-induced conditioned taste aversion (CTA), and conditioned place preference (CPP) reward remains unclear. The present study utilized the "pre- and post-association" experimental paradigm (2010) to test whether the rewarding and aversive properties of MAMPH can be modulated by an N-methyl-D-aspartic acid (NMDA) lesion in the NAc core. Moreover, it tested how an NAc core NMDA lesion affected the innate reward of saccharin solution intake. The results demonstrate that MAMPH could simultaneously induce an aversive CTA and a rewarding CPP effect, supporting the paradoxical effect hypothesis of abused drugs, in particular amphetamine. Meanwhile, the NMDA-lesioned NAc core increased the reward effect of CPP but did not alter the aversive CTA effect. The NAc core NMDA lesion also enhanced the innate reward of saccharin solution intake. The NAc core therefore seemingly plays an inhibitory role in the innate reward of saccharin solution intake and in the CPP effect. The paradoxical effect hypothesis of abused drugs provides some explanations for the present data in the case of MAMPH administrations. The NAc core may play an essential role in modulating the rewarding but not the aversive properties of MAMPH. The present findings could contribute to the understanding and eventual advancement of clinical interventions for drug addiction and the development of novel pharmacological treatments.