Action of Delta-9-tetrahydrocannabinol on GABA(A) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampal slice

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Abstract

We have investigated the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, and the selective GABAA receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 mu M, respectively. Responses to both of these agonists were selectively reduced by the noncompetitive GABAA antagonist picrotoxin (5 mu M), but were unaffected by the GABAB antagonist 2-hydroxy-saclofen (500 mu M). Responses evoked by the selective GABAB receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 mu M), potentiated responses to GABA, but not to muscimol. Similarly, 10-1000 nM Delta-9-THC had no significant effect on the response to muscimol, whereas 1000 nM Delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but muscimol is not, the results are consistent with the suggestion that Delta-9-THC inhibits the uptake of GABA in the hippocampus. (C) 1997 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1387-1392
Number of pages6
JournalNeuropharmacology
Volume36
Issue number10
DOIs
Publication statusPublished - 1997

Keywords

  • Delta-9-tetrahydrocannabinol
  • cannabinoids
  • GABA
  • muscimol
  • baclofen
  • uptake
  • BRAIN CANNABINOID RECEPTOR
  • NEUROTRANSMITTER UPTAKE
  • MOUSE-BRAIN
  • CATALEPSY
  • CELLS
  • CHLORDIAZEPOXIDE
  • SYNAPTOSOMES
  • ANTAGONIST
  • MUSCIMOL
  • MICE

Cite this

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title = "Action of Delta-9-tetrahydrocannabinol on GABA(A) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampal slice",
abstract = "We have investigated the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, and the selective GABAA receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 mu M, respectively. Responses to both of these agonists were selectively reduced by the noncompetitive GABAA antagonist picrotoxin (5 mu M), but were unaffected by the GABAB antagonist 2-hydroxy-saclofen (500 mu M). Responses evoked by the selective GABAB receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 mu M), potentiated responses to GABA, but not to muscimol. Similarly, 10-1000 nM Delta-9-THC had no significant effect on the response to muscimol, whereas 1000 nM Delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but muscimol is not, the results are consistent with the suggestion that Delta-9-THC inhibits the uptake of GABA in the hippocampus. (C) 1997 Elsevier Science Ltd.",
keywords = "Delta-9-tetrahydrocannabinol, cannabinoids, GABA, muscimol, baclofen, uptake, BRAIN CANNABINOID RECEPTOR, NEUROTRANSMITTER UPTAKE, MOUSE-BRAIN, CATALEPSY, CELLS, CHLORDIAZEPOXIDE, SYNAPTOSOMES, ANTAGONIST, MUSCIMOL, MICE",
author = "Coull, {Moyra A.} and Johnston, {Andrew Thomas} and Pertwee, {Roger Guy} and Davies, {Stephen Nicholas}",
year = "1997",
doi = "10.1016/S0028-3908(97)00110-X",
language = "English",
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journal = "Neuropharmacology",
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T1 - Action of Delta-9-tetrahydrocannabinol on GABA(A) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampal slice

AU - Coull, Moyra A.

AU - Johnston, Andrew Thomas

AU - Pertwee, Roger Guy

AU - Davies, Stephen Nicholas

PY - 1997

Y1 - 1997

N2 - We have investigated the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, and the selective GABAA receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 mu M, respectively. Responses to both of these agonists were selectively reduced by the noncompetitive GABAA antagonist picrotoxin (5 mu M), but were unaffected by the GABAB antagonist 2-hydroxy-saclofen (500 mu M). Responses evoked by the selective GABAB receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 mu M), potentiated responses to GABA, but not to muscimol. Similarly, 10-1000 nM Delta-9-THC had no significant effect on the response to muscimol, whereas 1000 nM Delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but muscimol is not, the results are consistent with the suggestion that Delta-9-THC inhibits the uptake of GABA in the hippocampus. (C) 1997 Elsevier Science Ltd.

AB - We have investigated the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, and the selective GABAA receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 mu M, respectively. Responses to both of these agonists were selectively reduced by the noncompetitive GABAA antagonist picrotoxin (5 mu M), but were unaffected by the GABAB antagonist 2-hydroxy-saclofen (500 mu M). Responses evoked by the selective GABAB receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 mu M), potentiated responses to GABA, but not to muscimol. Similarly, 10-1000 nM Delta-9-THC had no significant effect on the response to muscimol, whereas 1000 nM Delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but muscimol is not, the results are consistent with the suggestion that Delta-9-THC inhibits the uptake of GABA in the hippocampus. (C) 1997 Elsevier Science Ltd.

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KW - BRAIN CANNABINOID RECEPTOR

KW - NEUROTRANSMITTER UPTAKE

KW - MOUSE-BRAIN

KW - CATALEPSY

KW - CELLS

KW - CHLORDIAZEPOXIDE

KW - SYNAPTOSOMES

KW - ANTAGONIST

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KW - MICE

U2 - 10.1016/S0028-3908(97)00110-X

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