Correlation between cannabinoid mediated effects on paired pulse depression and induction of long term potentiation in the rat hippocampal slice

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Abstract

Cannabinoids cause an increase in synaptic transmission via gamma-aminobutyric acid (GABA) receptors and this may be the mechanism by which activation of CBI receptors blocks the induction of long-term potentiation (LTP). To test this hypothesis, we used paired pulse depression (PPD) of CA1 population spike responses recorded in the rat hippocampal slice as an index of GABA-ergic feedback inhibition, to establish whether the effects of a stereoselective CB1 receptor agonist on GABA-ergic transmission and LTP were correlated. The active isomer, WIN55212-2, blocked the induction of LTP and suppressed PPD over the concentration range-250 nM-5 mu M, whereas the inactive isomer, WIN55212-3, was inactive at 5 mu M. The effects of 5 mu M WIN55212-2 on both LTP and PPD were completely blocked by the CB1 receptor antagonist SR141716A (5 mu M). The results show that the effects are correlated in that both suppression of PPD and blockade of induction of LTP are probably mediated by CB1 receptors. However, the suppression in PPD suggests that WIN55212-2 caused a decrease in GABA-ergic feedback transmission which would be expected to facilitate, rather than block, the induction of LTP. We therefore conclude that the blockade of LTP by cannabinoids is not via upregulation of GABA-ergic synaptic transmission. (C) 1998 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1123-1130
Number of pages8
JournalNeuropharmacology
Volume37
Issue number9
DOIs
Publication statusPublished - Sep 1998

Keywords

  • WIN55212-2
  • SR141716A
  • cannabinoids
  • paired pulse depression
  • gamma-aminobutyric acid
  • METABOTROPIC GLUTAMATE RECEPTORS
  • ENANTIOMERIC CANNABINOIDS
  • NEUROTRANSMITTER UPTAKE
  • GABAERGIC TRANSMISSION
  • SELECTIVE ANTAGONIST
  • BRAIN SYNAPTOSOMES
  • INVERSE AGONIST
  • GLOBUS-PALLIDUS
  • MODULATION
  • CATALEPSY
  • WIN55 212-2
  • ¿-Aminobutyric acid

Cite this

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title = "Correlation between cannabinoid mediated effects on paired pulse depression and induction of long term potentiation in the rat hippocampal slice",
abstract = "Cannabinoids cause an increase in synaptic transmission via gamma-aminobutyric acid (GABA) receptors and this may be the mechanism by which activation of CBI receptors blocks the induction of long-term potentiation (LTP). To test this hypothesis, we used paired pulse depression (PPD) of CA1 population spike responses recorded in the rat hippocampal slice as an index of GABA-ergic feedback inhibition, to establish whether the effects of a stereoselective CB1 receptor agonist on GABA-ergic transmission and LTP were correlated. The active isomer, WIN55212-2, blocked the induction of LTP and suppressed PPD over the concentration range-250 nM-5 mu M, whereas the inactive isomer, WIN55212-3, was inactive at 5 mu M. The effects of 5 mu M WIN55212-2 on both LTP and PPD were completely blocked by the CB1 receptor antagonist SR141716A (5 mu M). The results show that the effects are correlated in that both suppression of PPD and blockade of induction of LTP are probably mediated by CB1 receptors. However, the suppression in PPD suggests that WIN55212-2 caused a decrease in GABA-ergic feedback transmission which would be expected to facilitate, rather than block, the induction of LTP. We therefore conclude that the blockade of LTP by cannabinoids is not via upregulation of GABA-ergic synaptic transmission. (C) 1998 Elsevier Science Ltd. All rights reserved.",
keywords = "WIN55212-2, SR141716A, cannabinoids, paired pulse depression, gamma-aminobutyric acid, METABOTROPIC GLUTAMATE RECEPTORS, ENANTIOMERIC CANNABINOIDS, NEUROTRANSMITTER UPTAKE, GABAERGIC TRANSMISSION, SELECTIVE ANTAGONIST, BRAIN SYNAPTOSOMES, INVERSE AGONIST, GLOBUS-PALLIDUS, MODULATION, CATALEPSY, WIN55 212-2, ¿-Aminobutyric acid",
author = "Paton, {Gaynor S.} and Pertwee, {Roger Guy} and Davies, {Stephen Nicholas}",
year = "1998",
month = "9",
doi = "10.1016/S0028-3908(98)00096-3",
language = "English",
volume = "37",
pages = "1123--1130",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",
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TY - JOUR

T1 - Correlation between cannabinoid mediated effects on paired pulse depression and induction of long term potentiation in the rat hippocampal slice

AU - Paton, Gaynor S.

AU - Pertwee, Roger Guy

AU - Davies, Stephen Nicholas

PY - 1998/9

Y1 - 1998/9

N2 - Cannabinoids cause an increase in synaptic transmission via gamma-aminobutyric acid (GABA) receptors and this may be the mechanism by which activation of CBI receptors blocks the induction of long-term potentiation (LTP). To test this hypothesis, we used paired pulse depression (PPD) of CA1 population spike responses recorded in the rat hippocampal slice as an index of GABA-ergic feedback inhibition, to establish whether the effects of a stereoselective CB1 receptor agonist on GABA-ergic transmission and LTP were correlated. The active isomer, WIN55212-2, blocked the induction of LTP and suppressed PPD over the concentration range-250 nM-5 mu M, whereas the inactive isomer, WIN55212-3, was inactive at 5 mu M. The effects of 5 mu M WIN55212-2 on both LTP and PPD were completely blocked by the CB1 receptor antagonist SR141716A (5 mu M). The results show that the effects are correlated in that both suppression of PPD and blockade of induction of LTP are probably mediated by CB1 receptors. However, the suppression in PPD suggests that WIN55212-2 caused a decrease in GABA-ergic feedback transmission which would be expected to facilitate, rather than block, the induction of LTP. We therefore conclude that the blockade of LTP by cannabinoids is not via upregulation of GABA-ergic synaptic transmission. (C) 1998 Elsevier Science Ltd. All rights reserved.

AB - Cannabinoids cause an increase in synaptic transmission via gamma-aminobutyric acid (GABA) receptors and this may be the mechanism by which activation of CBI receptors blocks the induction of long-term potentiation (LTP). To test this hypothesis, we used paired pulse depression (PPD) of CA1 population spike responses recorded in the rat hippocampal slice as an index of GABA-ergic feedback inhibition, to establish whether the effects of a stereoselective CB1 receptor agonist on GABA-ergic transmission and LTP were correlated. The active isomer, WIN55212-2, blocked the induction of LTP and suppressed PPD over the concentration range-250 nM-5 mu M, whereas the inactive isomer, WIN55212-3, was inactive at 5 mu M. The effects of 5 mu M WIN55212-2 on both LTP and PPD were completely blocked by the CB1 receptor antagonist SR141716A (5 mu M). The results show that the effects are correlated in that both suppression of PPD and blockade of induction of LTP are probably mediated by CB1 receptors. However, the suppression in PPD suggests that WIN55212-2 caused a decrease in GABA-ergic feedback transmission which would be expected to facilitate, rather than block, the induction of LTP. We therefore conclude that the blockade of LTP by cannabinoids is not via upregulation of GABA-ergic synaptic transmission. (C) 1998 Elsevier Science Ltd. All rights reserved.

KW - WIN55212-2

KW - SR141716A

KW - cannabinoids

KW - paired pulse depression

KW - gamma-aminobutyric acid

KW - METABOTROPIC GLUTAMATE RECEPTORS

KW - ENANTIOMERIC CANNABINOIDS

KW - NEUROTRANSMITTER UPTAKE

KW - GABAERGIC TRANSMISSION

KW - SELECTIVE ANTAGONIST

KW - BRAIN SYNAPTOSOMES

KW - INVERSE AGONIST

KW - GLOBUS-PALLIDUS

KW - MODULATION

KW - CATALEPSY

KW - WIN55 212-2

KW - ¿-Aminobutyric acid

U2 - 10.1016/S0028-3908(98)00096-3

DO - 10.1016/S0028-3908(98)00096-3

M3 - Article

VL - 37

SP - 1123

EP - 1130

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 9

ER -