Involvement of the nucleus accumbens shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors

Neuropharmacology. 2013 Aug:71:112-23. doi: 10.1016/j.neuropharm.2013.03.017. Epub 2013 Apr 6.

Abstract

Background: Nucleus accumbens (NAc) and prefrontal cortex (PFC) dopaminergic and glutamatergic systems are involved in fear/anxiety-related behaviors; meanwhile NAc dopaminergic system activity is mediated by PFC via NAc glutamatergic projections. This study has investigated the involvement of NAc shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors.

Method: Elevated plus-maze apparatus was employed to test parameters of anxiety-like behaviors in male Wistar rats.

Results: Unilateral intra-prelimbic injection of NMDA (0.9 μg/μl) but not D-AP7 (NMDA receptor antagonist; 0.25, 0.5 and 1 μg/μl) induced anxiolytic-like behaviors which was blocked by D-AP7. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1 μg/μl) and quinpirole (dopamine D2 receptor agonist; 0.125, 0.25 and 0.5 μg/μl) into the left NAc shell, did not alter anxiety-like behaviors. However, injection of SKF38393 (dopamine D1 receptor agonist; 3 μg/μl) and sulpiride (dopamine D2 receptor antagonist; 0.4 and 0.6 μg/μl) into the left NAc shell, likewise induced anxiolytic-like behaviors which were blocked by SCH23390 (0.25 μg/μl) and SKF96365 (Ca-channel blocker; 0.125 μg/μl)/SCH23390 (0.25 μg/μl), respectively. Furthermore, infusion of the subthreshold dose of SCH23390 (0.25 μg/μl) or quinpirole (0.25 μg/μl) into the left NAc shell, reduced while did not alter intra-prelimbic NMDA-induced anxiolytic-like behaviors, respectively. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1 μg/μl) or sulpiride (0.2 μg/μl), potentiated the lower dose response, while decreased the higher dose intra-left prelimbic NMDA response.

Conclusion: Our results suggested a modulatory effect of the NAc shell dopaminergic system on prelimbic NMDA-induced anxiolytic-like behaviors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy
  • Anxiety / metabolism*
  • Behavior, Animal / drug effects
  • Disease Models, Animal*
  • Dopamine / chemistry
  • Dopamine / metabolism*
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / adverse effects
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Injections, Intraventricular
  • Male
  • N-Methylaspartate
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Protein Isoforms / agonists
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / chemistry
  • Receptors, Dopamine / metabolism*

Substances

  • Dopamine Agonists
  • Dopamine Antagonists
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Receptors, Dopamine
  • N-Methylaspartate
  • Dopamine