Long-term potentiation-like facilitation through GABAA receptor blockade in the mouse dentate gyrus in vivo.
We have investigated the characteristics of a long-term potentiation (LTP)-like facilitation in vivo through GABAA receptor blockade in C57BL/6 and Alzheimer-model transgenic mice dentate gyrus. Bicuculline induced the 'LTP-like' facilitation in a dose-dependent manner. MK-801 inhibited the induction but not maintenance of 'LTP-like' facilitation through bicuculline. Tetanic LTP was further enhanced by bicuculline, but the 'LTP-like' facilitation was conversely attenuated by tetanus. In transgenic mice expressing mutant human tau as an Alzheimer-model, the 'LTP-like' facilitation through bicuculline was significantly greater than tetanic LTP. Bicuculline recovered tetanic LTP impaired in these transgenic mice. These results suggest that GABAA receptor blockade plays an important role in learning and memory, providing a clue for the clinical use of GABAA antagonists to improve cognitive disorders.
Matsuyama
Shogo
S
Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji, Japan. shogo@himeji-du.ac.jp
Taniguchi
Taizo
T
Kadoyama
Keiichi
K
Matsumoto
Akira
A
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000235:genetics / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D016875:tau Proteins; D016291:Dizocilpine Maleate; D001640:Bicuculline