Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice

Behav Brain Res. 2014 Mar 15:261:114-26. doi: 10.1016/j.bbr.2013.12.007. Epub 2013 Dec 12.

Abstract

Background and aim: The critical role of cannabinoidergic and serotonergic systems of the amygdala in modulation of anxiety-like behaviors and emotional memory has already been demonstrated. The present study aimed to investigate the possible role of the basolateral amygdala (BLA) 5-HT3 and 5-HT4 serotonergic systems upon ACPA (CB1 cannabinoid receptor agonist)-induced anxiolytic-like behaviors and emotional memory impairment using the elevated plus-maze (EPM) test-retest paradigm in male mice.

Method: bilateral guide-cannulae were implanted to allow intra-BLA microinjection of serotonergic agents.

Results: the intraperitoneal injection of ACPA could induce anxiolytic-like behaviors and reduce the emotional memory formation. Intra-BLA injection of M-Chlorophenylbiguanide (M-Chl, a 5-HT3 serotonin receptor agonist) neither altered the anxiety-like behaviors nor the emotional memory formation by itself, while the higher dose of Y-25130 (a 5-HT3 serotonin receptor antagonist) reduced the emotional memory formation and locomotor activity but not the anxiety-like behaviors. Furthermore, injection of a higher dose of RS67333 and RS23597 (as 5-HT4 serotonin receptor agonist and antagonist, respectively) did not alter the anxiety-like behaviors, while reduced the emotional memory formation. In addition, the intra-BLA injection of M-Chl but not Y-25130 and RS67333 restored the ACPA-induced anxiolytic-like behaviors and emotional memory deficit, while a higher dose of RS67333 decreased the locomotor activity. Moreover, the intra-BLA microinjection of RS23597 could restore the ACPA-induced anxiolytic-like behaviors but not the emotional memory deficit.

Conclusion: based on our findings, ACPA seems to induce its anxiolytic-like behaviors and emotional memory formation deficits via activation and deactivation of the BLA 5-HT4 and 5-HT3 serotonin receptors.

Keywords: Anxiety; Elevated plus-maze; Emotional memory; Mouse; Serotonergic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Analysis of Variance
  • Animals
  • Anxiety Disorders / chemically induced*
  • Arachidonic Acids / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced*
  • Mice
  • Microinjections
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Receptors, Serotonin, 5-HT4 / metabolism*
  • Serotonin Agents / pharmacology

Substances

  • Arachidonic Acids
  • Receptor, Cannabinoid, CB1
  • Receptors, Serotonin, 5-HT3
  • Serotonin Agents
  • arachidonylcyclopropylamide
  • Receptors, Serotonin, 5-HT4