GABAA receptors modulate cannabinoid-evoked hypothermia.

Abstract

Cannabinoids evoke hypothermia by stimulating central CB(1) receptors. GABA induces hypothermia via GABA(A) or GABA(B) receptor activation. CB(1) receptor activation increases GABA release in the hypothalamus, a central locus for thermoregulation, suggesting that cannabinoid and GABA systems may be functionally linked in body temperature regulation. We investigated whether GABA receptors modulate the hypothermic actions of [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one] (WIN 55212-2), a selective cannabinoid agonist, in male Sprague-Dawley rats. WIN 55212-2 (2.5 mg/kg im) produced a rapid hypothermia that peaked 45-90 min postinjection. The hypothermia was attenuated by bicuculline (2 mg/kg ip), a GABA(A) antagonist. However, SCH 50911 (1-10 mg/kg ip), a GABA(B) blocker, did not antagonize the hypothermia. Neither bicuculline (2 mg/kg) nor SCH 50911 (10 mg/kg) by itself altered body temperature. We also investigated a possible role for CB(1) receptors in GABA-generated hypothermia. Muscimol (2.5 mg/kg ip), a GABA(A) agonist, or baclofen (5 mg/kg ip), a GABA(B) agonist, evoked a significant hypothermia. Blockade of CB(1) receptors with SR141716A (2.5 mg/kg im) did not antagonize muscimol- or baclofen-induced hypothermia, indicating that GABA-evoked hypothermia does not contain a CB(1)-sensitive component. Our results implicate GABA(A) receptors in the hypothermic actions of cannabinoids and provide further evidence of a functional link between cannabinoid and GABA systems.

• Authors: S M Rawls, R J Tallarida, D A Kon, E B Geller, Martin W Adler
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 78 Issue 1 Pg. 83-91 (May 2004) ISSN: 0091-3057 [Print] United States
• PMID: 15159137 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzoxazines
• Cannabinoids
• GABA Agonists
• GABA Antagonists
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• Morpholines
• Naphthalenes
• Receptor, Cannabinoid, CB1
• Receptors, GABA-A
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone

Topics

• Animals
• Benzoxazines
• Cannabinoids (toxicity)
• GABA Agonists (pharmacology)
• GABA Antagonists (pharmacology)
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• Hypothermia (chemically induced, physiopathology)
• Male
• Morpholines (pharmacology)
• Naphthalenes (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (agonists, physiology)
• Receptors, GABA-A (physiology)