Synergistic effect between prelimbic 5-HT3 and CB1 receptors on memory consolidation deficit in adult male Sprague-Dawley rats: An isobologram analysis

Neuroscience. 2016 Mar 11;317:173-83. doi: 10.1016/j.neuroscience.2015.12.010. Epub 2015 Dec 14.


The serotonergic system has often been defined as a neuromodulator system, and is specifically involved in learning and memory via its various receptors. Serotonin is involved in many of the same processes affected by cannabinoids. The present study investigated the influence of bilateral post-training intra-prelimbic (PL) administrations of serotonergic 5-hydroxytryptamine type-3 (5-HT3) receptor agents on arachidonylcyclopropylamide (ACPA) (cannabinoid CB1 receptor agonist)-induced amnesia, using the step-through inhibitory avoidance (IA) task to assess memory in adult male Sprague-Dawley rats. The results indicated that sole intra-PL microinjection of ACPA (0.1 and 0.5 μg/rat) and 5-HT3 serotonin receptor agonist (m-Chlorophenylbiguanide hydrochloride, m-CPBG; 0.001, 0.01 and 0.1 μg/rat) impaired, whereas Y-25130 (a selective 5-HT3 serotonin receptor antagonist; 0.001 and 0.01 and 0.1 μg/rat) did not alter IA memory consolidation, by itself. Moreover, intra-PL administration of subthreshold dose of m-CPBG (0.0005 μg/rat) potentiated, while Y-25130 (0. 1 μg/rat) restored ACPA-induced memory consolidation deficit. The isobologram analysis showed that there is a synergistic effect between ACPA and m-CPBG on memory consolidation deficit. These findings suggest that 5-HT3 receptor mechanism(s), at least partly, play(s) a role in modulating the effect of ACPA on memory consolidation in the PL area.

Keywords: ACPA; Y-25130; inhibitory avoidance (IA) memory; m-CPBG; pre-limbic area.

MeSH terms

  • Animals
  • Arachidonic Acids / toxicity
  • Avoidance Learning / drug effects
  • Biguanides / toxicity
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cannabinoid Receptor Agonists / toxicity
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism*
  • Motor Activity / drug effects
  • Oxazines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Serotonin Antagonists / toxicity
  • Serotonin Receptor Agonists / toxicity


  • Arachidonic Acids
  • Biguanides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cannabinoid Receptor Agonists
  • Oxazines
  • Receptor, Cannabinoid, CB1
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • arachidonylcyclopropylamide
  • azasetron
  • 1-(3-chlorophenyl)biguanide