The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation

Behav Brain Res. 2008 Dec 16;195(1):112-9. doi: 10.1016/j.bbr.2007.11.023. Epub 2007 Dec 7.

Abstract

Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Dose-Response Relationship, Drug
  • Indoles / administration & dosage
  • Indoles / pharmacology
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Phenols / administration & dosage
  • Phenols / pharmacology
  • Piperazines / administration & dosage
  • Piperazines / pharmacology
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology
  • Pyridines / administration & dosage
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / physiology*
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology

Substances

  • 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole
  • AS 19 compound
  • Indoles
  • Phenols
  • Piperazines
  • Pyrazoles
  • Pyridines
  • Receptors, Serotonin
  • SB 269970
  • SB 399885
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • Tetrahydronaphthalenes
  • serotonin 6 receptor
  • serotonin 7 receptor
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide