Involvement of the nucleus accumbens shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors.

Background: Nucleus accumbens (NAc) and prefrontal cortex (PFC) dopaminergic and glutamatergic systems are involved in fear/anxiety-related behaviors; meanwhile NAc dopaminergic system activity is mediated by PFC via NAc glutamatergic projections. This study has investigated the involvement of NAc shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors.

Method: Elevated plus-maze apparatus was employed to test parameters of anxiety-like behaviors in male Wistar rats.

Results: Unilateral intra-prelimbic injection of NMDA (0.9 μg/μl) but not D-AP7 (NMDA receptor antagonist; 0.25, 0.5 and 1 μg/μl) induced anxiolytic-like behaviors which was blocked by D-AP7. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1 μg/μl) and quinpirole (dopamine D2 receptor agonist; 0.125, 0.25 and 0.5 μg/μl) into the left NAc shell, did not alter anxiety-like behaviors. However, injection of SKF38393 (dopamine D1 receptor agonist; 3 μg/μl) and sulpiride (dopamine D2 receptor antagonist; 0.4 and 0.6 μg/μl) into the left NAc shell, likewise induced anxiolytic-like behaviors which were blocked by SCH23390 (0.25 μg/μl) and SKF96365 (Ca-channel blocker; 0.125 μg/μl)/SCH23390 (0.25 μg/μl), respectively. Furthermore, infusion of the subthreshold dose of SCH23390 (0.25 μg/μl) or quinpirole (0.25 μg/μl) into the left NAc shell, reduced while did not alter intra-prelimbic NMDA-induced anxiolytic-like behaviors, respectively. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1 μg/μl) or sulpiride (0.2 μg/μl), potentiated the lower dose response, while decreased the higher dose intra-left prelimbic NMDA response.

Conclusion: Our results suggested a modulatory effect of the NAc shell dopaminergic system on prelimbic NMDA-induced anxiolytic-like behaviors.