Effects of NMDA receptor antagonists on olfactory learning and memory in the honeybee (Apis mellifera)

Pharmacol Biochem Behav. 2004 Feb;77(2):191-7. doi: 10.1016/j.pbb.2003.09.023.


In contrast to vertebrates the involvement of glutamate and N-methyl-D-aspartate (NMDA) receptors in brain functions in insects is both poorly understood and somewhat controversial. Here, we have examined the behavioural effects of two noncompetitive NMDA receptor antagonists, memantine (low affinity) and MK-801 (high affinity), on learning and memory in honeybees (Apis mellifera) using the olfactory conditioning of the proboscis extension reflex (PER). We induced memory deficit by injecting harnessed individuals with a glutamate transporter inhibitor, L-trans-2,4-PDC (L-trans-2,4-pyrrolidine dicarboxylate), that impairs long-term (24 h), but not short-term (1 h), memory in honeybees. We show that L-trans-2,4-PDC-induced amnesia is 'rescued' by memantine injected either before training, or before testing, suggesting that memantine restores memory recall rather than memory formation or storage. When injected alone memantine has a mild facilitating effect on memory. The effects of MK-801 are similar to those of L-trans-2,4-PDC. Both pretraining and pretesting injections lead to an impairment of long-term (24 h) memory, but have no effect on short-term (1 h) memory of an olfactory task. The implications of our results for memory processes in the honeybee are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bees / physiology*
  • Cyclohexenes
  • Dicarboxylic Acids / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Learning / drug effects*
  • Limonene
  • Memantine / pharmacology
  • Memory / drug effects*
  • Mental Recall / drug effects
  • Neural Pathways / drug effects
  • Pyrrolidines / pharmacology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Smell / drug effects*
  • Terpenes / pharmacology


  • Cyclohexenes
  • Dicarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • Pyrrolidines
  • Receptors, N-Methyl-D-Aspartate
  • Terpenes
  • Dizocilpine Maleate
  • pyrrolidine-2,4-dicarboxylic acid
  • Limonene
  • Memantine