An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol

Roger Guy Pertwee, S E Browne, C D Stretton, T M Ross

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.

Original languageEnglish
Pages (from-to)581-585
Number of pages5
JournalPharmacology, Biochemistry & Behavior
Volume40
Issue number3
DOIs
Publication statusPublished - Nov 1991

Keywords

  • DELTA-9-THC
  • CANNABIDIOL
  • BENZODIAZEPINE
  • FLURAZEPAM
  • PENTYLENETETRAZOLE
  • GAMMA-AMINOBUTYRIC ACID
  • MICE
  • BODY TEMPERATURE
  • HYPOTHERMIA
  • ANTINOCICEPTION
  • ANTICONVULSANT EFFECT
  • GUINEA PIG ISOLATED ILEUM
  • DRUGS
  • CATALEPSY
  • ACID
  • delta-9-THC
  • cannabidiol
  • benzodiazepine
  • flurazepam
  • pentyleneterazole
  • gamma-aminobutryic acid
  • mice
  • body-temperature
  • hypothermia
  • antinociception
  • anticonvulsant effect
  • guinea pig isolated ileum

Cite this

An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol. / Pertwee, Roger Guy; Browne, S E ; Stretton, C D ; Ross, T M.

In: Pharmacology, Biochemistry & Behavior, Vol. 40, No. 3, 11.1991, p. 581-585.

Research output: Contribution to journalArticle

@article{58953313d85848128a4177075533ace8,
title = "An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol",
abstract = "Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.",
keywords = "DELTA-9-THC, CANNABIDIOL, BENZODIAZEPINE, FLURAZEPAM, PENTYLENETETRAZOLE, GAMMA-AMINOBUTYRIC ACID, MICE, BODY TEMPERATURE, HYPOTHERMIA, ANTINOCICEPTION, ANTICONVULSANT EFFECT, GUINEA PIG ISOLATED ILEUM, DRUGS, CATALEPSY, ACID, delta-9-THC, cannabidiol, benzodiazepine, flurazepam, pentyleneterazole, gamma-aminobutryic acid, mice, body-temperature, hypothermia, antinociception, anticonvulsant effect, guinea pig isolated ileum",
author = "Pertwee, {Roger Guy} and Browne, {S E} and Stretton, {C D} and Ross, {T M}",
year = "1991",
month = "11",
doi = "10.1016/0091-3057(91)90366-A",
language = "English",
volume = "40",
pages = "581--585",
journal = "Pharmacology, Biochemistry & Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol

AU - Pertwee, Roger Guy

AU - Browne, S E

AU - Stretton, C D

AU - Ross, T M

PY - 1991/11

Y1 - 1991/11

N2 - Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.

AB - Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.

KW - DELTA-9-THC

KW - CANNABIDIOL

KW - BENZODIAZEPINE

KW - FLURAZEPAM

KW - PENTYLENETETRAZOLE

KW - GAMMA-AMINOBUTYRIC ACID

KW - MICE

KW - BODY TEMPERATURE

KW - HYPOTHERMIA

KW - ANTINOCICEPTION

KW - ANTICONVULSANT EFFECT

KW - GUINEA PIG ISOLATED ILEUM

KW - DRUGS

KW - CATALEPSY

KW - ACID

KW - delta-9-THC

KW - cannabidiol

KW - benzodiazepine

KW - flurazepam

KW - pentyleneterazole

KW - gamma-aminobutryic acid

KW - mice

KW - body-temperature

KW - hypothermia

KW - antinociception

KW - anticonvulsant effect

KW - guinea pig isolated ileum

U2 - 10.1016/0091-3057(91)90366-A

DO - 10.1016/0091-3057(91)90366-A

M3 - Article

VL - 40

SP - 581

EP - 585

JO - Pharmacology, Biochemistry & Behavior

JF - Pharmacology, Biochemistry & Behavior

SN - 0091-3057

IS - 3

ER -