The modulatory role of accumbens and hippocampus D2 receptors in anxiety and memory
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.
KeywordsElevated plus-maze Anxiety Aversive learning Dorsal hippocampus Accumbens Dopamine D2 receptors Rat
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.
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.
- Gianlorenco AC, Canto-de-Souza A, Mattioli R (2011) Microinjection of histamine into the cerebellar vermis impairs emotional memory consolidation in mice. Brain Res Bull 86:134–138. https://doi.org/10.1016/j.brainresbull.2011.05.014 CrossRefPubMedGoogle Scholar
- Kudolo J, Tabassum H, Frey S et al (2010) Electrical and pharmacological manipulations of the nucleus accumbens core impair synaptic plasticity in the dentate gyrus of the rat. Neuroscience 168:723–731. https://doi.org/10.1016/j.neuroscience.2010.04.015 CrossRefPubMedGoogle Scholar
- LaLumiere RT, Nawar EM, McGaugh JL (2005) Modulation of memory consolidation by the basolateral amygdala or nucleus accumbens shell requires concurrent dopamine receptor activation in both brain regions. Learn Mem 12:296–301. https://doi.org/10.1101/lm.93205 CrossRefPubMedPubMedCentralGoogle Scholar
- Nazari-Serenjeh F, Rezayof A (2013) Cooperative interaction between the basolateral amygdala and ventral tegmental area modulates the consolidation of inhibitory avoidance memory. Prog Neuro-Psychopharmacology Biol Psychiatry 40:54–61. https://doi.org/10.1016/j.pnpbp.2012.10.003 CrossRefGoogle Scholar
- Nazari-Serenjeh F, Rezayof A, Zarrindast MR (2011) Functional correlation between GABAergic and dopaminergic systems of dorsal hippocampus and ventral tegmental area in passive avoidance learning in rats. Neuroscience 196:104–114. https://doi.org/10.1016/j.neuroscience.2011.08.073 CrossRefPubMedGoogle Scholar
- Packard MG, White NM (1989) Memory facilitation produced by dopamine agonists: role of receptor subtype and mnemonic requirements. Pharmacol Biochem Behav 33:511–518Google Scholar
- Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier, New York, NYGoogle Scholar
- Stern CA, Do Monte FH, Gazarini L et al (2010) Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest. Neuroscience 170:214–222. https://doi.org/10.1016/j.neuroscience.2010.06.080 CrossRefPubMedGoogle Scholar
- Tan SE (2008) Roles of hippocampal NMDA receptors and nucleus accumbens D1 receptors in the amphetamine-produced conditioned place preference in rats. Brain Res Bull 77:412–419. https://doi.org/10.1016/j.brainresbull.2008.09.007 CrossRefPubMedGoogle Scholar