5-HT4 receptors improve social olfactory memory in the rat

Neuropharmacology. Apr-May 1997;36(4-5):681-7. doi: 10.1016/s0028-3908(96)00169-4.

Abstract

Serotonin (5-HT) is involved in a large variety of physiological functions and it appears now that it could play a role in cognitive processes through the activation of 5-HT4 receptors. The present study was conducted to determine the effect of BIMU1, a mixed 5-HT4 agonist/5-HT3 antagonist on social olfactory recognition in rats, a behaviour test which has previously been shown to access short-term memory and to be sensitive to cholinergic drugs. This test is based on the investigation of an unfamiliar juvenile by an adult rat during two distinct 5-min presentations. At a 30-min delay after each presentation adults recognized the juvenile, whereas after a 2-hr delay all the adults had forgotten it. When administered intraperitoneally immediately after the first presentation, BIMU1 (10 mg/kg) enhanced short-term memory (i.e. recognition of the juvenile after a 2-hr delay). Ondansetron (10 and 100 micrograms/kg injected intraperitoneally), a 5-HT3 antagonist, had no significant effect on this form of memory. The effect of BIMU1 was antagonized by intraperitoneal injection of GR 125487, a very selective and potent 5-HT4 antagonist. The antagonistic effect was obtained at 1 and 10 mg/kg of GR 125487, but not at 0.1 mg/kg. It is certainly a specific effect on brain 5-HT4 receptors, since we determined a brain concentration of GR 125487 equal to 3.8 x 10(-7) M after the intraperitoneal injection of 10 mg/kg of this drug. This GR 125487 concentration is certainly sufficient to occupy all the 5-HT4 brain receptors (Kd = 10(-10) M) but not to occupy 5-HT3 receptors (Kd > 10(-6) M). The 5-HT4 specificity of the blockade by GR 125487 is further demonstrated by the fact that a 10-fold lower dose of GR 125487 (1 mg/kg) is also effective to inhibit the BIMU1 effect.

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology
  • Brain / drug effects
  • Brain / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Indoles / metabolism
  • Indoles / pharmacology
  • Male
  • Maze Learning / drug effects
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology*
  • Muscarinic Agonists / pharmacology
  • Muscarinic Antagonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Smell / drug effects
  • Smell / physiology*
  • Social Behavior*
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacology

Substances

  • Benzimidazoles
  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • (endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide
  • (endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide
  • GR 113808