Involvement of the nucleus accumbensshell presynaptic NMDA receptors on anxiolytic-like behaviors induced by NMDA in adult male Wistar rat

Glutamatergic system stimulationthe nucleus accumbens shell, may affect anxiety-related behaviors, aversive learning and memory. Glutamate receptors are differentially distributed in preand postsynaptic sites contributing to neuronal communications.The present study aimed to examine the possible involvement of the NAc shell presynaptic NMDA receptors on NMDA induced responses, using the elevated-plus maze (EPM) task in maleWistar rats. Bilateral guide cannulae were implanted to allow microinjection of glutamatergic agonist (NMDA) or ca +2 channel blocker (SKF96365 hydrochloride) agents. Pretest intra-NAc shell infusion of NMDA induced anxiolytic-like behaviors and impaired the EPM-associated memory upon test and retest, respectively. In addition our findings showed that, the intra-NAc shell infusion of Ca +2 channel blocker at applied doses, does not alter the anxiety-like response and aversive memory upon test and retest, respectively. Furthermore, infusing the subthreshold dose SKF prior to the injection of effective doses of NMDA, reduced the anxiolytic-like response and improved the aversive memory impairment which had already been induced by intra-NAc shell NMDA injection. Our study showed that,inhibition of the neurotransmitter exocytosis from pre-synaptic neuron via Ca +2 channel blockade bySKF96365 decreases affected induced by NMDA in the NAc shell region, indicating the involvement of the pre-synaptic NMDA receptors in NMDA induced responses.Therefore, NMDA's ability to increase anxiolytic-like behaviors and the aversive memory impairment may be the result of an action on pre-synaptic glutamatergic receptors which in turn decrease the glutamate effect at synaptic terminal level.