CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward.

摘要: Abstract The HIV-1 regulatory protein, trans-activator of transcription (Tat), interacts with opioids to potentiate neuroinflammation and neurodegeneration within the CNS. These effects may involve C-C chemokine receptor type 5 (CCR5); however, behavioral contribution CCR5 on Tat/opioid interactions is not known. Using a transgenic murine model that expresses Tat protein in GFAP-regulated, doxycycline-inducible manner, we assessed morphine tolerance, dependence, reward. To assess influence these effects, mice were pretreated oral vehicle or antagonist, maraviroc, prior administration. We found expression significantly attenuated antinociceptive potency acute (2–64 mg/kg, i.p.) non-tolerant mice. Consistent this, withdrawal symptoms among morphine-tolerant Pretreatment maraviroc blocked Tat, reinstating restoring symptomology Twenty-four hours following administration, potentiated (∼3.5-fold) morphine-conditioned place preference further (∼5.7-fold). Maraviroc exerted no measurable its own. Protein array analyses revealed only minor changes cytokine profiles when was administered acutely repeatedly; 24 h post several cytokines greatly increased, including endogenous ligands (CCL3, CCL4, CCL5), as well CCL2. elevated levels pretreatment effects. data demonstrate mediates key aspects Tat-induced alterations rewarding properties opioids.