Differential effects of 5-HT3 receptor antagonism on working memory failure due to deficiency of hippocampal cholinergic and glutamatergic transmission in rats

Brain Res. 1997 Jul 11;762(1-2):211-5. doi: 10.1016/s0006-8993(97)00448-4.


The muscarinic acetylcholine receptor antagonist scopolamine significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 3.2 microg/side into the dorsal hippocampus. Concurrent infusion of the selective and potent 5-hydroxytryptamine3 (5-HT3) receptor antagonist Y-25130 (0.32 and 1.0 microg/side) significantly attenuated the increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine. Intrahippocampal Y-25130 (1.0 microg/side) by itself did not affect working memory errors. On the other hand, intrahippocampal administration of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side caused a significant increase in the number of working memory errors. However, Y-25130 at 1.0 microg/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that antagonism of hippocampal 5-HT3 receptors is ineffective against working memory failure resulting from blockade of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory function of rats.

MeSH terms

  • Acetylcholine / physiology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Conditioning, Psychological / drug effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / physiology
  • Hippocampus / chemistry
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Male
  • Memory / drug effects*
  • Muscarinic Antagonists / pharmacology
  • Oxazines / pharmacology*
  • Piperazines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT3
  • Scopolamine / pharmacology
  • Serotonin Antagonists / pharmacology*
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Antagonists
  • Muscarinic Antagonists
  • Oxazines
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Glutamic Acid
  • azasetron
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Scopolamine
  • Acetylcholine