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Activation of matrix metalloproteinase in dorsal hippocampus drives improvement in spatial working memory after intra‐ VTA nicotine infusion in rats
Author(s) -
Shu Hui,
Zheng Guoqing,
Wang Xiaona,
Sun Yanyun,
Liu Yushan,
Weaver John Michael,
Shen Xianzhi,
Liu Wenlan,
Jin Xinchun
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13283
Subject(s) - ventral tegmental area , nicotine , hippocampus , neuroscience , substantia nigra , spontaneous alternation , dopaminergic , chemistry , dopamine , psychology
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.Our study showed the brain region and mechanism underlying nicotine‐induced spatial working memory improvement. In response to nicotine treatment, VTA‐hippocampus circuit is activated and MMP‐9 activation in dorsal hippocampus mediates the memory improvement. Our data suggest nicotine increases spatial working memory by activating MMP‐9 in dorsal hippocampus. Nicotine improves spatial working memory by enhancing an ability to use Win‐shift strategy and increasing correct choice. This effect is mediated by the VTA‐hippocampus circuit and MMP‐9 in dHPC is activated with intra‐VTA nicotine infusion in rats.