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.
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Hui
H
Shu
Department of Neurology, The Second Affiliated Hospital &Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Guo-qing
GQ
Zheng
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Xiaona
X
Wang
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Yanyun
Y
Sun
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Yushan
Y
Liu
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.|Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
John Michael
JM
Weaver
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Xianzhi
X
Shen
The Central Laboratory, Shenzhen Key Laboratory of Neurosurgery, and the Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, China.
Wenlan
W
Liu
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Xinchun
X
Jin
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D008845:Microinjections; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects*; D017557:Ventral Tegmental Area
C095170:4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D018722:Nicotinic Agonists; D009842:Oligopeptides; D009538:Nicotine; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
matrix metalloproteinase; nicotine; rat; spatial working memory; ventral tegmental area