Effects of 5-HT4 receptor agonists and antagonists in learning

Pharmacol Biochem Behav. 1997 Mar;56(3):347-51. doi: 10.1016/s0091-3057(96)00224-9.

Abstract

In the present work, the effects of pre- or post-training (ip) injection of BIMU1 and BIMU8 (5-HT4 agonists) were figured out in the autoshaping learning task. Furthermore, the post-training effects of these agonists after treatment with SDZ 205-557 and GR 125487D (5-HT4 antagonists) or p-Chloroamphetamine (PCA) were also explored. Animals were individually trained in a lever-press response on the autoshaping task and 24 hours later were tested. The results showed that pre-training injection of BIMU1 (5 20 mg/Kg) or BIMU8 (20 mg/Kg) increased the CR; in contrast, the post-training administration of BIMU1 (10-20 mg/Kg) or BIMU8 (5 and 20 mg/Kg) decreased it. Further experiments revealed that the post-training injections of SDZ 205-557 (1.0-10.0 mg/Kg) or GR 125487D (0.39-1.56 mg/Kg) by themselves did not alter the CR. When BIMU1 or BIMU8 was administered to rats pretreated with SDZ 205-557 (10 mg/Kg) or GR 125487D (0.78 mg/Kg), the decrement induced by 5-HT4 the agonists was reversed; in contrast, the administration of PCA failed to modify the CR or the agonist-induced responses. The findings showed that the pre-training stimulation of 5-HT4 receptors enhanced the acquisition of CR, while, post-training activation of 5-HT4 receptors, impaired the consolidation of learning. The latter effect was not altered by PCA pretreatment. The data show that 5-HT4 receptors are involved in the acquisition and consolidation of learning. It seems that postsynaptic 5-HT4 receptors are involved in the latter effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Conditioning, Operant / drug effects*
  • Drug Evaluation, Preclinical
  • Male
  • Rats
  • Rats, Wistar
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • p-Chloroamphetamine / pharmacology

Substances

  • Benzimidazoles
  • Bridged Bicyclo Compounds, Heterocyclic
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • (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
  • p-Chloroamphetamine