Activation of matrix metalloproteinase in dorsal hippocampus drives improvement in spatial working memory after intra- VTA nicotine infusion in rats.

The hippocampus receives dopaminergic projections from the ventral tegmental area ( VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences hippocampus-dependent behaviors. Enhancements in working memory performance have been previously reported following acute smoking/nicotine exposure. However, the underlying mechanism remains unclear. This study investigated the effects of nicotine on spatial working memory ( SWM) and the mechanisms involved. Delayed alternation T-maze task was used to assess SWM. In situ and gel gelatin zymography were used to detect matrix metalloproteinase-9 ( MMP-9) in SWM. Systemic or local (intra- VTA) administration of nicotine significantly improves SWM, which was accompanied by increased MMP-9 activity in dorsal hippocampus ( dHPC). Intra- dHPC administration of MMP inhibitor FN-439 abolished the memory enhancement induced by intra- VTA nicotine infusion. FN-439 had no effect on locomotor behavior. Our data suggest that intra- VTA nicotine infusion activates MMP-9 in dHPC to improve SWM in rats. [ABSTRACT FROM AUTHOR]