Cannabinoid‐induced working memory impairment is reversed by a second generation cholinesterase inhibitor in rats

  title={Cannabinoid‐induced working memory impairment is reversed by a second generation cholinesterase inhibitor in rats},
  author={Daniela Braida and Mariaelvina Sala},
Cannabinoids which impair rat working memory appear to inhibit hippocampal extracellular acetylcholine (Ach) release and reduce choline uptake through an interaction with CB1 cannabinoid receptors. Here we report that CP 55,940, a potent bicyclic synthetic cannabinoid analog, dose–dependently impaired rat performance, when given i.p. 20 min before an eight-arm radial maze test. The selective CB1 cannabinoid receptor antagonist SR 141716A, given i.p. 20 min earlier, significantly reduced the… 

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

The notion that cannabinoid-modulated cholinergic activity is a mechanism underlying the performance deficits in DNMS is supported, whether deficits are due to reduced nicotinic or muscarinic receptor activation, or both, awaits further analysis.

Cannabinoids alter recognition memory in rats.

First evidence that cannabinoids impair recognition memory in rats is found, as a stable analogue of endogenous cannabinoid anandamide and a potent CB(1) receptor agonist, CP 55,940 significantly attenuated recognition memory.

Hippocampal endocannabinoids inhibit spatial learning and limit spatial memory in rats

Systemic Rimonabant-induced deficits are due to anxiogenic properties of the drug and the possibility that selective inactivation of hippocampal CB1 receptors may be memory enhancing is discussed.

Cannabinoids and prefrontal cortical function: Insights from preclinical studies

The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex: an in vivo and in vitro study.

In vivo and in vitro findings suggest an increase in cortical glutamatergic transmission by CB(1) receptors, an effect that may underlie some of the psychoactive and behavioural actions of acute exposure to marijuana.

Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats

The results suggest that the stimulation of CB1 receptors in the prefrontal cortex, amygdala, and hippocampus with the subsequent activation of different signaling pathways is the first event underlying the effects of cannabinoids on anxious states.

Endocannabinoids in cognition and dependence.

Converging evidence in which performance in a variety of memory tasks is enhanced following either SR141716A treatment or in CB(1) receptor knockout mice indicates that this system may play an important role in modulating cognition.



Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A.

The results suggest that cannabinoid receptor activation can produce a strong inhibition of ACh release in the hippocampus, and suggests that this compound is an inverse agonist at cannabinoid receptors or it is antagonizing the actions of an endogenous ligand acting on these receptors.

Effects of delta-9-tetrahydrocannabinol on delayed match to sample performance in rats: alterations in short-term memory associated with changes in task specific firing of hippocampal cells.

Findings strongly suggest that performance of the DMTS task was selectively impaired by the lack of Sample phase discharge of hippocampal neurons during theDMTS trial, and that this effect could serve as the basis for the well characterized short-term memory and other cognitive deficits reported in humans after smoking marijuana.

Dimen KR and Martin BR

  • Psychopharmacology 119,
  • 1995

Effects of delta 9-tetrahydrocannabinol and cannabidiol on sodium-dependent high affinity choline uptake in the rat hippocampus.

The results suggest that the septal-hippocampal cholinergic tract is a major site of action of delta 9-THC and may provide a neurochemical basis for the differential pharmacological properties of delta 8-Tetrahydrocannabinol and CBD.

Handbook of Experimental Pharmacology: Pharmacological Aspects of Drug Dependence

  • 1996

Acknowledgements: This study was supported by grant from Ministero della Ricerca Scienti®ca e Tecnologica

  • Pharmacol Biochem Behav 32,
  • 1989