Diazepam inhibits HIV-1 Tat-induced migration of human microglia

During HIV-1 encephalitis, the chemotaxis-inducing activity of Tat may enha nce the viral life cycle through recruitment of additional susceptible micr oglial cells to foci of infection. Benzodiazepines (BDZs) readily penetrate the blood-brain barrier and are known to possess anti-inflammatory propert ies. Pretreatment of human microglial cells with peripheral (Ro5-4864) and mixed (diazepam), but not central (clonazepam), benzodiazepine receptor lig ands was found to potently suppress HIV-1 Tat-induced chemotaxis. Applicati on of Tat to microglial cells evokes an increase in intracellular calcium c oncentration ([Ca2+](i)) that rapidly desensitizes the cells. Diazepam's in hibitory effect was associated with its ability to block Tat-induced [Ca2+] (i) mobilization. These data support the notion that through their effects on microglia, peripheral BDZ receptor ligands could alter the neuropathogen esis of HIV-1.