title: Chronic scopolamine-injection-induced cognitive deficit on reward-directed instrumental learning in rat is associated with CREB signaling activity in the cerebral cortex and dorsal hippocampus.
abstract: BACKGROUND
  Scopolamine, a nonselective muscarinic receptor antagonist, has been used in experimental animal models of dementia. It has been demonstrated to disrupt performances in a battery of behavioral tests. However, no attempt has been made to determine how scopolamine-treated animals would respond to a series of reward-directed instrumental learning (RDIL) tasks.
  
  
  OBJECTIVE
  The present study was designed to investigate the effects of chronic intraperitoneal injection of scopolamine in Wistar rats on RDIL, as well as on the expression of memory-related molecules in the dorsal hippocampus (DH) and cerebral cortex (CCx).
  
  
  METHODS
  The effects of the pretraining injection of scopolamine on the acquisition of instrumental response (experiment 1) were first investigated. Then, the effects of post-training manipulation on the maintenance of instrumental response and the responses to changes in contingency degradation and signal discrimination were assessed (experiment 2). Finally, the expression of cyclic AMP response element-binding protein (CREB), phosphorylated CREB, and brain-derived neurotrophic factor in the DH and CCx were examined using Western blotting and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The acquisition of instrumental conditioning is more vulnerable than its maintenance. The 3.0-mg/kg dose of scopolamine rendered rats unable to make adaptive changes in facing contingency degradation and correct responses in signal discrimination tasks. Furthermore, CREB signaling was inactivated by pretraining scopolamine treatment in both the DH and CCx. Nevertheless, this pathway was selectively suppressed by post-training treatment only in the CCx during memory reconsolidation.
  
  
  CONCLUSIONS
  The results suggest that scopolamine-induced cognitive deficits on RDIL are related to the distinguishing alteration of CREB signaling in the DH and CCx.
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.forename: Sidi
authors.initials: S
authors.lastname: Li
authors.forename: Shanguang
authors.initials: S
authors.lastname: Chen
authors.forename: Xiuping
authors.initials: X
authors.lastname: Sun
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zeng
authors.forename: Yiran
authors.initials: Y
authors.lastname: He
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced*; D003216:Conditioning, Operant / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012601:Scopolamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018727:Muscarinic Antagonists; D012601:Scopolamine