Cannabinoid and cholinergic systems interact during performance of a short-term memory task in the rat

Anushka V. Goonawardena, Lianne Robinson, Robert E. Hampson, Gernot Riedel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


It is now well established that cannabinoid agonists such as Delta(9)-tetrahydrocannabinol (THC), anandamide, and WIN 55,212-2 (WIN-2) produce potent and specific deficits in working memory (WM)/short-term memory (STM) tasks in rodents. Although mediated through activation of CB1 receptors located in memory-related brain regions such as the hippocampus and prefrontal cortex, these may, in part, be due to a reduction in acetylcholine release (i.e., cholinergic hypofunction). To determine the interaction between cannabinoid and cholinergic systems, we exposed rats treated with WIN-2 or cholinergic drugs to a hippocampal-dependent delayed nonmatch to sample (DNMS) task to study STM, and recorded hippocampal single-unit activity in vivo. WIN-2 induced significant deficits in DNMS performance and reduced the average firing and bursting rates of hippocampal principal cells through a CB1 receptor-mediated mechanism. Rivastigmine, an acetylcholinesterase inhibitor, reversed these STM deficits and normalized hippocampal discharge rates. Effects were specific to 1 mg/kg WIN-2 as rivastigmine failed to reverse the behavioral and physiological deficits that were observed in the presence of MK-801, an NMDA receptor antagonist. This supports the notion that cannabinoid-modulated cholinergic activity is a mechanism underlying the performance deficits in DNMS. Whether deficits are due to reduced nicotinic or muscarinic receptor activation, or both, awaits further analysis.

Original languageEnglish
Pages (from-to)502-511
Number of pages10
JournalLearning & memory
Issue number10
Early online date28 Sept 2010
Publication statusPublished - Oct 2010


  • Delta(9)-tetrahydrocannabinol
  • brain slices
  • impairs spatial memory
  • 8-arm radial maze
  • receptor-mediated inhibition
  • sample performance
  • hippocampal acetylcholine-release
  • SR 141716A
  • in-vivo
  • endocannabinoid system


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