Early morphine exposure reduced viral burden in the periphery and induced regional difference in brains of LP-BM5 MAIDS model

Abstract

Intravenous opioid use contributes to 11% of HIV infections in the U.S.A. Morphine suppresses the immune system while exacerbating the progression of HIV. To investigate morphine effects on HIV-associated neurocognitive disorders (HAND), we used the LP-BM5 infection murine AIDS (MAIDS) model. Previously, we found that morphine exposure at 7 wks post-infection (p.i.) enhanced cognitive impairment associated with MAIDS, increased hippocampal viral loads, and decreased CCL5 expression in examined brain regions, without affecting peripheral immunodeficiency. Because many HIV+ patients are exposed to opioids before infection, we examined these parameters after exposing the animals to morphine before and immediately after infection. Male mice were implanted with two placebo or 25mg morphine pellets for 6 days, with infection occurring on post-pellet implantation day 3. At 7 wks p.i., cognitive impairment was assessed by the spontaneous alternation T-maze task. At wk 8, blood, spleen and brain regions (hippocampus, striatum and frontal lobe) were harvested. LP-BM5 induced splenomegaly and higher levels of serum IgG2a and IgM, regardless of morphine treatment. Morphine significantly decreased body weight-normalized spleen weight. Morphine did not alter viral BM5Def RNA in spleen or any brain region examined. Morphine appeared to reduce LP-BM5-induced CCL5 expression in the striatum and frontal lobe. LP-BM5 alone appeared to increase the expression of both IFN-α and IFN-β in the frontal lobe only. Infection or morphine exposure did not affect animals’ performance in the T-maze task. Together with our previous results, these results suggest that timing of morphine exposure can alter the modulation and progression of MAIDS and HAND.