To investigate the effect of opiates on human immunodeficiency virus type 1 (HIV-1)-related neuronal apoptosis, primary human fetal neuronal/glial cell cultures were exposed to gp120 IIIB in the absence and the presence of morphine. Although morphine by itself had little effect on neuronal survival, the combination of morphine (≥10 -7 mol/L) and gp120 IIIB (1 nmol/L) significantly increased neuronal apoptosis. The mechanism whereby morphine potentiates gp120 IIIB-induced neuronal apoptosis appears to involve activation of the p38 mitogen-activated protein kinase intracellular signaling pathway and microglial cells dispersed within the neuronal/glial cell cultures. These results provide additional insight into the molecular basis whereby opiate abuse could promote HIV-1-associated dementia.
Bibliographical noteFunding Information:
Received 16 August 2004; accepted 29 September 2004; electronically published 10 February 2005. Financial support: US Public Health Service (grant DA-04381). Reprints or correspondence: Dr. Phillip K. Peterson, Div. of Infectious Diseases and International Medicine, Dept. of Medicine, Hennepin County Medical Center, 701 Park Ave., Minneapolis, MN 55415 (email@example.com).