Pharmacological effects of cannabinoids on learning and memory in Lymnaea

Hiroshi Sunada, Takayuki Watanabe, Dai Hatakeyama, Sangmin Lee, Jeremy Forest, Manabu Sakakibara, Etsuro Ito*, Ken Lukowiak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Cannabinoids are hypothesized to play an important role in modulating learning andmemory formation. Here,we identifiedmRNAs expressed in Lymnaea stagnalis central nervous system that encode two G-protein-coupled receptors (Lymnaea CBr-like 1 and 2) that structurally resemble mammalian cannabinoid receptors (CBrs). We found that injection of a mammalian CBr agonist WIN 55,212-2 (WIN 55) into the snail before operant conditioning obstructed learning and memory formation. This effect of WIN 55 injection persisted for at least 4 days following its injection. A similar obstruction of learning and memory occurred when a severe traumatic stimulus was delivered to L. stagnalis. In contrast, injection of a mammalian CBr antagonist AM 251 enhanced long-term memory formation in snails and reduced the duration of the effects of the severe traumatic stressor on learning and memory. Neither WIN 55 nor AM 251 altered normal homeostatic aerial respiratory behaviour elicited in hypoxic conditions. Our results suggest that putative cannabinoid receptors mediate stressful stimuli that alter learning and memory formation in Lymnaea. This is also the first demonstration that putative CBrs are present in Lymnaea and play a key role in learning and memory formation.

Original languageEnglish
Pages (from-to)3026-3038
Number of pages13
JournalJournal of Experimental Biology
Issue number17
Publication statusPublished - 2017 Sept 1


  • Aerial respiratory behaviour
  • Cannabinoid
  • Long-term memory
  • Lymnaea stagnalis
  • Operant conditioning

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Molecular Biology
  • Insect Science


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