Effect of nucleus accumbens shell 5-HT4 receptors on the impairment of ACPA-induced emotional memory consolidation in male Wistar rats

Behav Pharmacol. 2016 Feb;27(1):12-21. doi: 10.1097/FBP.0000000000000174.


The present study investigates the effects of 5-HT4 receptors of the nucleus accumbens (NAc) shell on the impairment of emotional memory consolidation induced by cannabinoid CB1 receptor stimulation. The elevated plus maze test-retest paradigm was used to assess memory in adult male Wistar rats. Intra-NAc shell administration of ACPA (selective cannabinoid CB1 receptor agonist 0.006 µg/rat) and RS23597 (5-HT4 receptor antagonist 0.01 µg/rat), immediately after training, decreased emotional memory consolidation, suggesting a drug-induced amnesia, whereas post-training intra-NAc shell microinjections of RS67333 (5-HT4 receptor agonist 0.016 µg/rat) increased emotional memory consolidation. Interestingly, RS67333 exerted a dual effect on ACPA-induced behaviors, potentiating and restoring amnesia caused by the subthreshold and effective doses of ACPA, respectively. However, neither RS23597 nor AM251 (CB1 receptor antagonist 30, 60 and 120 ng/rat) affected emotional memory consolidation. Nonetheless, a subthreshold dose of AM251 (120 ng/rat) reversed the amnesia induced by ACPA (0.006 µg/rat) and RS23597 (0.01 µg/rat). None of the above doses altered the locomotor activity. In conclusion, our results suggest that the NAc-shell 5-HT4 receptors are involved in the modulation of ACPA-induced amnesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Arachidonic Acids
  • Cannabinoid Receptor Antagonists / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Emotions / drug effects
  • Emotions / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology*
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism*
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nootropic Agents / pharmacology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Random Allocation
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptors, Serotonin, 5-HT4 / metabolism*
  • Serotonin 5-HT4 Receptor Agonists / pharmacology


  • Aniline Compounds
  • Arachidonic Acids
  • Cannabinoid Receptor Antagonists
  • Cnr1 protein, rat
  • Nootropic Agents
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Serotonin 5-HT4 Receptor Agonists
  • arachidonylcyclopropylamide
  • Receptors, Serotonin, 5-HT4
  • RS 67333
  • AM 251