Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain.
OBJECTIVE
The chemokine, stromal cell-derived growth factor-1alpha (SDF-1alpha/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.


METHODS
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.


RESULTS
WIN 55,212-2 (5-15 microg) evoked a dose-related hypothermia, which was attenuated by SDF-1alpha/CXCL12 microinjected directly into the POAH. The inhibitory effect of SDF-1alpha/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-1alpha/CXCL12, acting at its receptor, CXCR4.


CONCLUSIONS
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.
Benamar
Khalid
K
Center for Substance Abuse Research, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA. kbenamar@temple.edu
Yondorf
Menachem
M
Geller
Ellen B
EB
Eisenstein
Toby K
TK
Adler
Martin W
MW
D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000819:agonists / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000502:physiology*
D048588:Benzoxazines; D002186:Cannabinoids; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D009025:Morpholines; D009281:Naphthalenes; D019718:Receptors, CXCR4; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone