Abstract

Introduction:  The  hippocampus  and  nucleus  accumbens  dopaminergic  (DAergic)  system  has  been implicated in cognitive functions such as anxiety, learning and memory. To clarify the interaction between dorsal hippocampal (DH) and  nucleus  accumbens (NAc) DAergic  system in  the  acquisition  of anxiety-like behavior  and  aversive  learning, the  effect  of  sulpiride,  as  a  DAergic  D2-like  receptor  antagonist, and co-injection  of this  drug into  these  structures were studied  on  the  acquisition  of anxiety-like  behavior  and aversive learning using an elevated plus-maze (EPM) test-retest paradigm in the male Wistar rats.  Materials and methods: Unilateral guide cannulae were implanted to allow microinjection of sulpiride.  Results: Pretest microinjection of sulpiride (0.125-0.5µg/rat) into the NAc increased the percentage of time spent in open-arms (%OAT), suggesting anxiolytic-like response. However, the control group rats displayed experience-induced  increases  in  open-arm  avoidance  when  retested  in  the  EPM,  suggesting  the  storing  of aversive  information  about  the  maze  was  preserved.  In  contrast,  sulpiride-treated  rats  failed  further avoidance  to  open-arms,  indicating  aversive  learning  deficit.  Moreover, pretest  microinjection  of  sulpiride (0.25-1  µg/rat) into  the  DH produced  no  anxiety- or  anxiolytic-like  effect  but  impaired  aversive  learning. Furthermore,  subthreshold  dose  of  sulpiride  into  both  sites  induced  anxiolytic-like  effect  and  aversive learning deficit.  Conclusion: Our data suggest involvement of D2 receptors in dopaminergic system interaction between DH and NAc regulating anxiety-related behaviors and EPM associative memory.