Gabaergic interneurons are the targets of cannabinoid actions in the humanhippocampus

Citation
I. Katona et al., Gabaergic interneurons are the targets of cannabinoid actions in the humanhippocampus, NEUROSCIENC, 100(4), 2000, pp. 797-804
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
0306-4522 → ACNP
Volume
100
Issue
4
Year of publication
2000
Pages
797 - 804
Database
ISI
SICI code
0306-4522(2000)100:4<797:GIATTO>2.0.ZU;2-7
Abstract
Cannabinoids have been shown to disrupt memory processes in mammals includi ng humans. Although the CB1 neuronal cannabinoid receptor was identified se veral years ago, neuronal network mechanisms mediating cannabinoid effects are still controversial in animals, and even more obscure in humans. In the present study, the localization of CB1 receptors was investigated at the c ellular and subcellular levels in the human hippocampus, using control post mortem and epileptic lobectomy tissue. The latter tissue was also used for [H-3]GABA release experiments, testing the predictions of the anatomical d ata. Detectable expression of CB1 was confined to interneurons, most of whi ch were found to be cholecystokinin-containing basket cells, CB1-positive c ell bodies showed immunostaining in their perinuclear cytoplasm, but not in their somadendritic plasmamembrane. CB1- immunoreactive axon terminals den sely covered the entire hippocampus, forming symmetrical synapses character istic of GABAergic boutons. Human temporal lobectomy samples were used in t he release experiments, as they were similar to the controls regarding cell ular and subcellular distribution of CB1 receptors. We found-1 that the CB1 receptor agonist, WIN 55,212-2, strongly reduced (H-3]GABA release, and th is effect was fully prevented by the specific CB1 receptor antagonist SR 14 1716A. This unique expression pattern and the presynaptic modulation of GABA relea se suggests a conserved role for CB1 receptors in controlling inhibitory ne tworks of the hippocampus that are responsible for the generation and maint enance of fast and slow oscillatory patterns. Therefore, a likely mechanism by which cannabinoids may impair memory and associational processes is an alteration of the fine-tuning of synchronized, rhythmic population events. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.