title: GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels.
abstract: Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABA(A) receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in naïve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and the lowest levels were observed 9 h after the acquisition trial. In the passive avoidance task, bicuculline methiodide administration within 1 h of training but not after 3 h significantly increased latency time in the retention trial 24 h after the acquisition trial. Concomitantly, 1 h post-training administration of bicuculline methiodide, which enhanced memory consolidation, significantly increased mBDNF levels 9 h after training compared to those of the vehicle-treated control group. In addition, exogenous human recombinant BDNF (hrBDNF) administration 9 h after training into the hippocampal CA1 region facilitated memory consolidation confirming that the increase in mBDNF at around 9 h after training plays a key role in the enhancement of memory consolidation. Moreover, the increases in latency time and immediate early gene expressions by bicuculline methiodide or hrBDNF were significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings suggest that the increase in the level of mBDNF and its function during a restricted time window after training are required for the enhancement of memory consolidation by GABA(A) receptor blockade.
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Dongdaemoon-Gu, Seoul, Republic of Korea.
authors: Dong Hyun
authors: DH
authors: Kim
authors: Jong Min
authors: JM
authors: Kim
authors: Se Jin
authors: SJ
authors: Park
authors: Mudan
authors: M
authors: Cai
authors: Xiaotong
authors: X
authors: Liu
authors: Seungheon
authors: S
authors: Lee
authors: Chan Young
authors: CY
authors: Shin
authors: Jong Hoon
authors: JH
authors: Ryu
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage / Q000494:pharmacology; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D058787:GABA-A Receptor Antagonists; D026121:Indole Alkaloids; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; C017069:bicuculline methiodide; D000841:Anisomycin; C049985:staurosporine aglycone; D001640:Bicuculline