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Physiological evidence for interaction between the HIV‐1 co‐receptor CXCR4 and the cannabinoid system in the brain
Author(s) -
Benamar Khalid,
Yondorf Menachem,
Geller Ellen B,
Eisenstein Toby K,
Adler Martin W
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00285.x
Subject(s) - cannabinoid , cannabinoid receptor , agonist , thermoregulation , endocannabinoid system , hypothermia , receptor , preoptic area , pharmacology , chemistry , biology , neuroscience , hypothalamus , medicine , endocrinology , biochemistry
Background and purpose: The chemokine, stromal cell‐derived growth factor‐1α (SDF‐1α/CXCL12), a member of the CXC chemokine family, and the ligand for CXCR4, the co‐receptor involved in the entry of human immunodeficiency virus‐1 (HIV‐1), was tested for its possible interaction with a physiological response to a cannabinoid. Experimental approach: The cannabinoid agonist, an aminoalkylindole, (+)‐WIN 55,212‐2 [(4,5‐dihydro‐2‐methyl‐4(4‐morpholinylmethyl)‐1‐(1‐naphthalenyl‐carbonyl)‐6H‐pyrrolo[3,2,1ij]quinolin‐6‐one], was infused directly into the preoptic anterior hypothalamus (POAH), the primary brain area involved in thermoregulation. Key results: WIN 55,212‐2 (5–15 µg) evoked a dose‐related hypothermia, which was attenuated by SDF‐1α/CXCL12 microinjected directly into the POAH. The inhibitory effect of SDF‐1α/CXCL12 on WIN 55,212‐2‐induced hypothermia was reversed by 1,1′‐[1,4‐phenylenebis(methylene)]bis[1,4,8,11‐tetraazacyclotetradecane] octohydrobromide dihydrate, an antagonist of SDF‐1α/CXCL12, acting at its receptor, CXCR4. Conclusion and implications: This study provides the first in vivo evidence for a thermoregulatory interaction between the HIV‐1 co‐receptor and the cannabinoid system in the brain.