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 pre- and 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, NMDAʹs 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.