Roles of hippocampal NMDA receptors and nucleus accumbens D1 receptors in the amphetamine-produced conditioned place preference in rats

Abstract

There are glutamatergic projections from the hippocampus to the nucleus accumbens (NAc), which regulate DA transmission in this structure. To be precise, the ventral hippocampal (VH) glutamatergic neurons project to the nucleus accumbens shell region (NAcSh), whereas the dorsal hippocampus (DH) sends glutamatergic projections to the nucleus accumbens core region (NAcC). This study investigates the roles of hippocampal N-methyl- d-aspartate (NMDA) glutamate receptors and NAc type 1 dopamine receptor (D1) in amphetamine-produced conditioned place preference (AMPH-CPP) in rats. Our earlier reports showed that AMPH-CPP results in the enhancement of hippocampal CaMKII activity and it can be impaired by NMDA antagonist (AP5). In this study AMPH-CPP did not alter the NAc CaMKII activity, although AMPH-CPP was impaired by a blockade of D1 receptors (SCH23390) during conditioning. Moreover, inactivation of hippocampal area (dorsal hippocampus or ventral hippocampus) impaired AMPH-CPP, but its effect was diminished by the activation of D1 receptors in accumbal region (NAc core or NAc shell). By inactivating both DH and NAc core resulted in the disruption of rat’s CPP expression. However, the impaired CPP expression was recovered during the next testing session, suggesting the disruption of CPP expression was a short term effect. Moreover, the disruption of CPP expression was not exhibited if NAc core was not inactivated. Interestingly, the rats that received activation in VH but an inactivation in NAc shell before testing show impaired CPP expression compared to those received inactivation in both VH and NAc shell. DH activation plus an inactivation in NAc core before testing show a significantly higher rate of the weakening of AMPH-CPP expression. Similarly, an activation of VH plus an inactivation of NAc shell before testing also show a statistically significant lower CPP score on tests 3 and 4. These results, taken together, indicate that NMDA receptor activation in DH and VH have different enhancing effects on the AMPH-CPP as their innervations onto the different NAc regions are essential for AMPH-CPP establishment. If the deterioration of AMPH-CPP expression (or extinction process) resembles the formation of new learning, then this active process might have been facilitated by the hippocampal NMDA receptor activations during testing.