The hypothermic response of mice to delta-9-tetrahydrocannobinol is enhanced is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH-23390 or sulpiride

Roger Guy Pertwee, D Hedley, A S M McQueen, S M Gentleman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/ anterior hypothalamic area through a chronically implanted cannula (20 µg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22°C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 µg) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 µg/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alphaadrenoceptors.

Original languageEnglish
Pages (from-to)149-155
Number of pages7
JournalNeuropharmacology
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 1988

Keywords

  • delta-9-tetrahydrocannabinol
  • dopamine D1 antagonists
  • dopamine D2 antagonists
  • alphaadrenoceptor antagonists
  • body temperature
  • mice

Cite this

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title = "The hypothermic response of mice to delta-9-tetrahydrocannobinol is enhanced is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH-23390 or sulpiride",
abstract = "Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/ anterior hypothalamic area through a chronically implanted cannula (20 µg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22°C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 µg) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 µg/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alphaadrenoceptors.",
keywords = "delta-9-tetrahydrocannabinol, dopamine D1 antagonists, dopamine D2 antagonists, alphaadrenoceptor antagonists, body temperature, mice",
author = "Pertwee, {Roger Guy} and D Hedley and McQueen, {A S M} and Gentleman, {S M}",
year = "1988",
month = "2",
doi = "10.1016/0028-3908(88)90164-5",
language = "English",
volume = "27",
pages = "149--155",
journal = "Neuropharmacology",
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T1 - The hypothermic response of mice to delta-9-tetrahydrocannobinol is enhanced is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH-23390 or sulpiride

AU - Pertwee, Roger Guy

AU - Hedley, D

AU - McQueen, A S M

AU - Gentleman, S M

PY - 1988/2

Y1 - 1988/2

N2 - Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/ anterior hypothalamic area through a chronically implanted cannula (20 µg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22°C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 µg) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 µg/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alphaadrenoceptors.

AB - Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/ anterior hypothalamic area through a chronically implanted cannula (20 µg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22°C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 µg) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 µg/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alphaadrenoceptors.

KW - delta-9-tetrahydrocannabinol

KW - dopamine D1 antagonists

KW - dopamine D2 antagonists

KW - alphaadrenoceptor antagonists

KW - body temperature

KW - mice

U2 - 10.1016/0028-3908(88)90164-5

DO - 10.1016/0028-3908(88)90164-5

M3 - Article

VL - 27

SP - 149

EP - 155

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

ER -