Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase

Approximately 35% of HIV-infected subjects, both children and adults, exhib it alterations in the sleep-waking cycle. MV surface glycoprotein gp120 has been postulated to contribute to this abnormality. For example, it has bee n reported that HIVgp120 modifies sleep in freely-moving rats and that it a lso activates the ERK pathway in brain slices, The goal of this work was to determine if sleep changes induced by HIVgp120 in normal rats are mediated by the MAPK pathway. Our results show that a single intraventricular admin istration of HIVgp120 selectively increases REMS and that such an increase can be prevented by U0126, an inhibitor of ERK activating enzyme, MEK. In c ontrast, SB202190, a MAPK-p38 inhibitor, had no effect on HIVgp120-induced increase in REMS. These results suggest that HIVgp120 increases REMS in the rat by specifically affecting the ERK signal transduction pathway. (C) 200 1 Published by Elsevier Science B.V.