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PMID: 8872363 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Physiological and behavioural effects of the endogenous cannabinoid, arachidonylethanolamide (anandamide), in the rat.

British journal of pharmacology ·Vol. 119 ·No. 1 ·1996-09-00 ·Pages 107-14

Stein EA, Fuller SA, Edgemond WS, Campbell WB

Abstract

1. Arachidonylethanolamide (AEA; anandamide) has been isolated from mammalian brain and found to bind to, and is thought to be, an endogenous ligand for the cannabinoid receptor. In order to understand better its behavioural and physiological properties, we have examined its acute effects in unanaesthetized freely behaving rats. 2. Intravenous AEA caused dose-related decreases in locomotor behaviour, a pronounced hyperreflexia, and a moderate antinociceptive state. At doses between 3 and 30 mg kg-1, a dose-dependent hypothermia and profound, time-dependent cardiovascular changes were also observed. 3. An immediate bradycardia exceeding 50% was seen within 10-15 s of administration and lasted up to 11 min following the highest dose of the drug. In contrast, the change in mean arterial pressure was biphasic: an immediate 20% decrease in mean arterial pressure followed by a significant increase in blood pressure that lasted about 13 min after the highest dose. 4. These data demonstrate that AEA in the unanaesthetized rat exerts behavioural and physiological effects generally similar to those seen following natural cannabinoids and synthetic cannabimimetic agents and suggests a role for AEA in regulation of various physiological processes.

MeSH Terms
Analgesia Animals Anti-Inflammatory Agents, Non-Steroidal/pharmacology Arachidonic Acid/pharmacology Arachidonic Acids/administration & dosage,adverse effects,pharmacology Behavior, Animal/drug effects Blood Pressure/drug effects Calcium Channel Blockers/adverse effects,pharmacology Cannabinoids/metabolism,pharmacology Dose-Response Relationship, Drug Endocannabinoids Heart Rate/drug effects Hypothermia/chemically induced Indomethacin/pharmacology Male Polyunsaturated Alkamides Rats Rats, Sprague-Dawley
Chemicals
Anti-Inflammatory Agents, Non-Steroidal Arachidonic Acids Calcium Channel Blockers Cannabinoids Endocannabinoids Polyunsaturated Alkamides Arachidonic Acid anandamide Indomethacin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Stein E A
Department of Psychiatry, Medical College of Wisconsin, Milwaukee 53226, USA.
Fuller S A
Edgemond W S
Campbell W B
References (33)
33 references, click to expand
  1. Analgesic activity of 9 -tetrahydrocannabinol in the rat and mouse.
    Psychopharmacologia. 1972;25(3):275-80 PMID: 5044401
  2. The effects of morphine methadone and meperidine on some reflex responses of spinal animals to nociceptive stimulation.
    J Pharmacol Exp Ther. 1951 Feb;101(2):132-43 PMID: 14814606
  3. Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat.
    J Pharmacol Exp Ther. 1976 Mar;196(3):649-56 PMID: 4606
  4. Biphasic nature of the effects of delta9-tetrahydrocannabinol on body temperature and brain amines of the rat.
    Eur J Pharmacol. 1977 Nov 15;46(2):93-9 PMID: 590330
  5. Reduced hypotensive action of arachidonic acid in the spontaneously hypertensive rat.
    Hypertension. 1980 Sep-Oct;2(5):657-63 PMID: 6998871
  6. Investigations on behavioral effects of an extract of Cannabis sativa L. in the rat.
    Psychopharmacology (Berl). 1981;75(2):144-7 PMID: 6798604
  7. The effects of morphine and delta-9-tetrahydrocannabinol on motor activity in rats.
    Psychopharmacology (Berl). 1982;78(4):358-60 PMID: 6296906
  8. In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat.
    J Pharmacol Exp Ther. 1984 Jan;228(1):1-12 PMID: 6319664
  9. Structural requirements for cannabinoid-induced antinociceptive activity in mice.
    Life Sci. 1985 Apr 22;36(16):1523-30 PMID: 2984503
  10. Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man.
    Pharmacol Rev. 1986 Mar;38(1):21-43 PMID: 3012605
  11. Cannabinoid pharmacology.
    Pharmacol Rev. 1986 Jun;38(2):151-78 PMID: 3529128
  12. Determination and characterization of a cannabinoid receptor in rat brain.
    Mol Pharmacol. 1988 Nov;34(5):605-13 PMID: 2848184
  13. Cannabinoid receptor localization in brain.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6 PMID: 2308954
  14. Structure of a cannabinoid receptor and functional expression of the cloned cDNA.
    Nature. 1990 Aug 9;346(6284):561-4 PMID: 2165569
  15. The cannabinoid receptor: biochemical, anatomical and behavioral characterization.
    Trends Neurosci. 1990 Oct;13(10):420-3 PMID: 1700516
  16. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study.
    J Neurosci. 1991 Feb;11(2):563-83 PMID: 1992016
  17. Spinal and supraspinal components of cannabinoid-induced antinociception.
    J Pharmacol Exp Ther. 1991 Aug;258(2):517-23 PMID: 1650831
  18. Neuronal localization of cannabinoid receptors and second messengers in mutant mouse cerebellum.
    Brain Res. 1991 Jun 28;552(2):301-10 PMID: 1913192
  19. Ca(2+)-dependent release from rat brain of cannabinoid receptor binding activity.
    J Neurochem. 1992 Feb;58(2):780-2 PMID: 1729420
  20. Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):3825-9 PMID: 1315042
  21. Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry.
    Neuroscience. 1992;48(3):655-68 PMID: 1376455
  22. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
    Science. 1992 Dec 18;258(5090):1946-9 PMID: 1470919
  23. Localization of cannabinoid receptor mRNA in rat brain.
    J Comp Neurol. 1993 Jan 22;327(4):535-50 PMID: 8440779
  24. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent.
    Eur J Pharmacol. 1993 Feb 9;231(2):313-4 PMID: 8384116
  25. Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase.
    J Neurochem. 1993 Jul;61(1):352-5 PMID: 8515284
  26. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7656-60 PMID: 8395053
  27. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist.
    Biochem Pharmacol. 1993 Sep 1;46(5):791-6 PMID: 8373432
  28. Anandamide, an endogenous ligand of the cannabinoid receptor, induces hypomotility and hypothermia in vivo in rodents.
    Pharmacol Biochem Behav. 1993 Dec;46(4):967-72 PMID: 7906042
  29. Effects of anandamide on cannabinoid receptors in rat brain membranes.
    Biochem Pharmacol. 1994 Feb 11;47(4):711-5 PMID: 8129747
  30. The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice.
    J Pharmacol Exp Ther. 1994 Jul;270(1):219-27 PMID: 8035318
  31. Characterization of ligand binding to the cannabinoid receptor of rat brain membranes using a novel method: application to anandamide.
    J Neurochem. 1995 Feb;64(2):677-83 PMID: 7830060
  32. Novel antagonist implicates the CB1 cannabinoid receptor in the hypotensive action of anandamide.
    Eur J Pharmacol. 1995 May 24;278(3):279-83 PMID: 7589169
  33. Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure.
    J Pharmacol Exp Ther. 1975 Mar;192(3):497-505 PMID: 1168252
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1996.tb15683.x
Published
1996-09-00
Pages
107-14
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1915721
Subset
IM
Grants
NIDA NIH HHS · DA09465 · United States
NHLBI NIH HHS · HL37981 · United States
External Links
PubMed source DOI: 10.1111/j.1476-5381.1996.tb15683.x PMC Full Text View journal details
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