Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition

Norbert Hájos, T. Freund

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

One of the well-known effects of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only cloned cannabinoid receptor type in the CNS, are selectively expressed on the axon terminals of a subset of GABAergic inhibitory interneurons containing the neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release from presynaptic terminals, thereby increasing the excitability of principal cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the hippocampal excitatory axon terminals, which suppress glutamate release. These cannabinoid receptors have distinct pharmacological features compared to CB1, i.e. WIN 55,212-2 is an order of magnitude less potent in reducing glutamatergic transmission than in inhibiting GABAergic postsynaptic currents, and the novel receptor binds vanilloid receptor ligands. Thus, at least two different cannabinoid sensitive presynaptic receptors regulate network activity in the hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct action on pyramidal cell axon terminals.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalChemistry and Physics of Lipids
Volume121
Issue number1-2
DOIs
Publication statusPublished - Dec 31 2002

Fingerprint

Cannabinoid Receptors
Cannabinoids
Presynaptic Terminals
Cannabinoid Receptor CB1
Hippocampus
Interneurons
Presynaptic Receptors
TRPV Cation Channels
Synaptic Potentials
Pyramidal Cells
Cholecystokinin
G-Protein-Coupled Receptors
Neuropeptides
Short-Term Memory
gamma-Aminobutyric Acid
Neurotransmitter Agents
Glutamic Acid
Chemical activation
Pharmacology
Ligands

Keywords

  • CB1 receptor
  • GABA
  • Glutamate
  • Hippocampus
  • Knockout
  • Vanilloid

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition. / Hájos, Norbert; Freund, T.

In: Chemistry and Physics of Lipids, Vol. 121, No. 1-2, 31.12.2002, p. 73-82.

Research output: Contribution to journalArticle

@article{7a55eb56ee3349b2bd76256839abbe76,
title = "Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition",
abstract = "One of the well-known effects of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only cloned cannabinoid receptor type in the CNS, are selectively expressed on the axon terminals of a subset of GABAergic inhibitory interneurons containing the neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release from presynaptic terminals, thereby increasing the excitability of principal cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the hippocampal excitatory axon terminals, which suppress glutamate release. These cannabinoid receptors have distinct pharmacological features compared to CB1, i.e. WIN 55,212-2 is an order of magnitude less potent in reducing glutamatergic transmission than in inhibiting GABAergic postsynaptic currents, and the novel receptor binds vanilloid receptor ligands. Thus, at least two different cannabinoid sensitive presynaptic receptors regulate network activity in the hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct action on pyramidal cell axon terminals.",
keywords = "CB1 receptor, GABA, Glutamate, Hippocampus, Knockout, Vanilloid",
author = "Norbert H{\'a}jos and T. Freund",
year = "2002",
month = "12",
day = "31",
doi = "10.1016/S0009-3084(02)00149-4",
language = "English",
volume = "121",
pages = "73--82",
journal = "Chemistry and Physics of Lipids",
issn = "0009-3084",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition

AU - Hájos, Norbert

AU - Freund, T.

PY - 2002/12/31

Y1 - 2002/12/31

N2 - One of the well-known effects of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only cloned cannabinoid receptor type in the CNS, are selectively expressed on the axon terminals of a subset of GABAergic inhibitory interneurons containing the neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release from presynaptic terminals, thereby increasing the excitability of principal cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the hippocampal excitatory axon terminals, which suppress glutamate release. These cannabinoid receptors have distinct pharmacological features compared to CB1, i.e. WIN 55,212-2 is an order of magnitude less potent in reducing glutamatergic transmission than in inhibiting GABAergic postsynaptic currents, and the novel receptor binds vanilloid receptor ligands. Thus, at least two different cannabinoid sensitive presynaptic receptors regulate network activity in the hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct action on pyramidal cell axon terminals.

AB - One of the well-known effects of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only cloned cannabinoid receptor type in the CNS, are selectively expressed on the axon terminals of a subset of GABAergic inhibitory interneurons containing the neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release from presynaptic terminals, thereby increasing the excitability of principal cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the hippocampal excitatory axon terminals, which suppress glutamate release. These cannabinoid receptors have distinct pharmacological features compared to CB1, i.e. WIN 55,212-2 is an order of magnitude less potent in reducing glutamatergic transmission than in inhibiting GABAergic postsynaptic currents, and the novel receptor binds vanilloid receptor ligands. Thus, at least two different cannabinoid sensitive presynaptic receptors regulate network activity in the hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct action on pyramidal cell axon terminals.

KW - CB1 receptor

KW - GABA

KW - Glutamate

KW - Hippocampus

KW - Knockout

KW - Vanilloid

UR - http://www.scopus.com/inward/record.url?scp=0037207070&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037207070&partnerID=8YFLogxK

U2 - 10.1016/S0009-3084(02)00149-4

DO - 10.1016/S0009-3084(02)00149-4

M3 - Article

C2 - 12505692

AN - SCOPUS:0037207070

VL - 121

SP - 73

EP - 82

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

SN - 0009-3084

IS - 1-2

ER -