Blockade of cortical muscarinic but not NMDA receptors prevents a novel taste from becoming familiar

Eur J Neurosci. 2003 Apr;17(8):1556-62. doi: 10.1046/j.1460-9568.2003.02608.x.


Exposure to a novel taste solution in the rat is followed by a decrease in its intake known as neophobia. This effect gradually disappears, and consumption increases from the second presentation of the taste (attenuation of neophobia), reflecting that the animal learned that it is safe to drink it. Conversely, if gastric malaise is induced after first intake, the rat will develop a long-lasting aversion (conditioned taste aversion). Previous attempts to elucidate the physiological nature of taste memory trace stems only from procedures that require malaise to measure taste memory. Here we assess the relevance of both muscarinic and N-methyl-d-aspartate receptors, known to be involved in conditioned taste aversion, on taste memory using a nonaversive procedure (attenuation of neophobia learning). Attenuation of neophobia was impaired by the muscarinic receptor antagonist, scopolamine, microinjected 20 min before, immediately after or up to 2 h after the first taste experience, suggesting that muscarinic receptors are involved in the acquisition and consolidation of attenuation of neophobia learning. However, the N-methyl-d-aspartate receptor antagonist, d,l-2-amino-5-phosphonovaleric acid, did not affect attenuation of neophobia even when the same dose of the drug was able to disrupt conditioned taste aversion learning, which suggests that attenuation of neophobia learning would be independent of N-methyl-d-aspartate receptors activity in the insular cortex. The neophobic response induced by strong saccharin presentation was not affected by either of the treatments given, which rules out any impairment in taste perception. These results indicate that while cortical muscarinic receptors are important in the formation and consolidation of safe memory trace, N-methyl-d-aspartate receptor activity appears to be noncritical.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Injections, Intraventricular
  • Male
  • Memory / drug effects
  • Microinjections
  • Muscarinic Antagonists / pharmacology
  • Rats
  • Receptors, Muscarinic / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Saccharin
  • Scopolamine / administration & dosage
  • Scopolamine / pharmacology
  • Taste / drug effects
  • Taste / physiology*


  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Receptors, N-Methyl-D-Aspartate
  • 2-Amino-5-phosphonovalerate
  • Scopolamine
  • Saccharin