Role of 5-HT1-7 receptors in short- and long-term memory for an autoshaping task: intrahippocampal manipulations

Brain Res. 2007 May 25:1147:140-7. doi: 10.1016/j.brainres.2007.02.007. Epub 2007 Feb 8.

Abstract

It was previously reported that brain areas containing serotonin (5-hydroxytryptamine, 5-HT) receptors mediate memory consolidation as well as short (STM)- and long-term memory (LTM). Here the effects of systemic and intrahippocampal administration of 5-HT agonists and antagonists on an autoshaping learning task were explored, which requires hippocampal translation and transduction as well as 5-HT receptors expression. As previously reported ketamine (glutamatergic antagonist) and two well-known amnesic drugs, scopolamine (cholinergic antagonist) and dizocilpine (NMDA antagonist) impaired STM but not LTM; dizocilpine even improved the latter. Since ketamine produces hallucinations and impairs memory in humans, we address the question if well-known antipsychotic haloperidol and clozapine might affect STM deficit. Indeed, systemic administration of clozapine<haloperidol reversed the ketamine-STM deficit. Considering that clozapine and haloperidol are antagonists for dopaminergic D2 and 5-HT(1A/2A/6/7) receptors, systemic and intrahippocampal administration of 5-HT drugs were further explored. The ketamine STM-induced deficit was blocked by 8-OHDPAT (5-HT(1A/7) agonist) and SB-399885 (a 5-HT(6) antagonist) but not by 5-HT(1B), 5-HT(2) and 5-HT(7) antagonists, thus implicating 5-HT(1A/7) and 5-HT(6) receptors. These data also suggest that ketamine (at 10 mg/kg) represents a reliable pharmacological tool to explore memory deficits related to hippocampus and schizophrenia.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / pharmacology
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Drug Interactions
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Neurotransmitter Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin Agents / pharmacology

Substances

  • Antipsychotic Agents
  • Neurotransmitter Agents
  • Receptors, Serotonin
  • Serotonin Agents