Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 10, pp 1107–1118 | Cite as

The modulatory role of accumbens and hippocampus D2 receptors in anxiety and memory

  • Mohaddeseh Ebrahimi-GhiriEmail author
  • Mohammad Nasehi
  • Mohammad-Reza Zarrindast
Original Article


The present study investigated the role of dopamine D2 receptors (D2Rs) of the dorsal hippocampus (DH) and the nucleus accumbens (NAc) and the effect of their dopaminergic activities on anxiety-like behavior and aversive learning using a test-retest elevated plus-maze (EPM) paradigm in male Wistar rats. Guide cannulae were implanted to allow microinjection of D2R agonist quinpirole or antagonist sulpiride. The pre-test intra-NAc microinjection of quinpirole (0.0625–0.25 μg/rat) or sulpiride (0.125–0.5 μg/rat) increased the percentage of time spent in the open arms (%OAT) of EPM, suggesting an anxiolytic-like effect. However, an increase in open-arm avoidance was observed in the control rats when retested in the EPM, suggesting aversive information storage. Furthermore, a similar result was obtained in the quinpirole-treated rats. In contrast, the sulpiride-treated rats failed to demonstrate further open-arm avoidance, thus proposing an aversive learning deficit. The intra-DH microinjection of drugs alone induced an anxiolytic-like effect and learning deficit. The quinpirole (0.125 μg/rat) injected into each site had no effect on the response induced by sulpiride injected into another site. Finally, a subthreshold dose of quinpirole in both sites did not alter the %OAT; on the contrary, it preserved the aversive memory. The sulpiride induced an anxiolytic-like effect and a learning deficit. Our data suggests that the involvement of D2Rs in the interactions of DH-NAc dopaminergic system helps regulate anxiety-related behavior and EPM-associative memory.


Elevated plus-maze Anxiety Aversive learning Dorsal hippocampus Accumbens Dopamine D2 receptors Rat 


Author contribution

ME acquired the animal data and wrote the manuscript. MN and MZ were responsible for the study concept, design, and proteomics analysis, as well as assisted with the data analysis and interpretation of findings. All authors critically reviewed the content and approved the final version for publication.

Funding information

The authors wish to thank the Iran National Science Foundation (INSF) for providing financial support to this project.

Compliance with ethical standards

The study was carried out in accordance with ethical standards in all aspects.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mohaddeseh Ebrahimi-Ghiri
    • 1
    Email author
  • Mohammad Nasehi
    • 2
  • Mohammad-Reza Zarrindast
    • 3
    • 4
    • 5
  1. 1.Department of Biology, Faculty of SciencesUniversity of ZanjanZanjanIran
  2. 2.Cognitive and Neuroscience Research Center (CNRC)Islamic Azad University, Tehran Medical Sciences BranchTehranIran
  3. 3.Department of Pharmacology School of MedicineTehran University of Medical SciencesTehranIran
  4. 4.Institute for Cognitive Science Studies (ICSS)TehranIran
  5. 5.Iranian National Center for Addiction StudiesTehran University of Medical SciencesTehranIran

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