Sucrose reinforcement effects following inhibition of AMPA and NMDA‐type glutamate receptors in the ventromedial prefrontal cortex

Abstract

The glutamatergic system is purported to play an important role in the self‐administration of both drug and non‐drug reinforcers, such as sucrose. Sucrose‐experienced rats exhibit blunted glutamate release within the ventromedial prefrontal cortex (vmPFC) while cocaine‐experienced rats exhibit increased cue‐induced glutamate release within the vmPFC. While the behavioral phenomenon seems to be similar, there may be different mechanisms of glutamate in cocaine‐ and sucrose‐seeking. To address this question, this study investigated the role of vmPFC AMPA‐ and NMDA ‐type glutamate receptors in sucrose‐taking. For this, male and female Sprague‐Dawley rats were implanted with bilateral guide cannulae within the vmPFC and were trained to self‐administer sucrose pellets (6hr/day) for 10 days. Using a within‐subjects design, rats were microinjected (0.5 μl per side) with the GluA2‐lacking selective AMPA antagonist Naspm (40 μg), the non‐selective AMPA receptor antagonist NBQX (1 μg), the GluN2A‐selective NMDA antagonist PPPA (0.43 μg), the GluN2B‐selective NMDA antagonist TCN‐237 (0.002 μg) and the non‐selective NMDA receptor antagonist D‐AP5 (2.5 μg). Following each microinjection, rats underwent a 2‐hr test for sucrose self‐administration. In males, microinjection of D‐AP5 increased responding for sucrose reinforcement, while no significant effects were observed for the other compounds tested. While in females, there were no significant effects observed for any of the compounds tested. These results indicate that activation of NMDA receptors within the vmPFC suppress sucrose self‐administration in male rats, whereas AMPA receptors do not appear to be involved.