CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice

Behav Brain Res. 2016 Mar 15:301:84-95. doi: 10.1016/j.bbr.2015.12.023. Epub 2015 Dec 19.

Abstract

The endocannabinoid system, through the cannabinoid type 1 (CB1) and 2 (CB2) receptors modulates many physiological functions, including different aspects of memory-related processes. The aim of the present experiments was to explore the role of the endocannabinoid system, through CB1 receptors in the different stages of short-term (acquisition, retention and retrieval) and long-term (acquisition, consolidation and retrieval) memory-related responses, using the inhibitory avoidance (IA) test in mice. Our results revealed that an acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, impairs the short-term or/and long-term acquisition, retention/consolidation, retrieval memory and learning processes in the IA test in mice. In turn, in this test an acute injection of AM 251 (1 and 3mg/kg), a CB1 receptor antagonist, improves the short-term or/and long-term memory stages, described above. Moreover, this memory impairment induced by effective dose of oleamide (20mg/kg) is reversed by non-effective dose of AM 251 (0.25mg/kg) in the IA task, which proves the selectivity of oleamide to CB1 receptors and confirms that the CB1 receptor-related mechanism is one of the possible mechanisms, responsible for memory and learning responses. Obtained results provide clear evidence that the endocannabinoid system, through CB1 receptors, participates in the different stages of short- and long-term memory-related behavior. This knowledge may open in the future new possibilities for the development of CB-based therapies, especially for memory impairment human disorders.

Keywords: Cannabinoid receptor ligands; Different stages of memory; Endocannabinoid system; Inhibitory avoidance test; Mice; Short- and long-term memory.

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoid Receptor Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Inhibition, Psychological*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neuropsychological Tests
  • Oleic Acids / pharmacology
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism*

Substances

  • CNR1 protein, mouse
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Oleic Acids
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251
  • oleylamide