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Updated: Jun 22, 2026

A Rat Model of EcoHIV Brain Infection
Published on: January 21, 2021
Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain
Khalid Benamar1, Menachem Yondorf, Ellen B Geller
1Center for Substance Abuse Research, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA. kbenamar@temple.edu
Background And Purpose:
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.
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 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.
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.
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