PMID- 18321872
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20211203
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Print)
IS  - 1047-3211 (Linking)
VI  - 18
IP  - 11
DP  - 2008 Nov
TI  - Dopaminergic modulation of auditory cortex-dependent memory consolidation through 
      mTOR.
PG  - 2646-58
LID - 10.1093/cercor/bhn026 [doi]
AB  - Previous studies in the auditory cortex of Mongolian gerbils on discrimination 
      learning of the direction of frequency-modulated tones (FMs) revealed that 
      long-term memory formation involves activation of the dopaminergic system, 
      activity of the protein kinase mammalian target of rapamycin (mTOR), and protein 
      synthesis. This led to the hypothesis that the dopaminergic system might modulate 
      memory formation via regulation of mTOR, which is implicated in translational 
      control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 
      substantially improved gerbils' FM discrimination learning when administered 
      systemically or locally into the auditory cortex shortly before, shortly after, 
      or 1 day before conditioning. Although acquisition performance during initial 
      training was normal, the discrimination of FMs was enhanced during retraining 
      performed hours or days after agonist injection compared with vehicle-injected 
      controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, 
      and the protein synthesis blocker anisomycin suppressed this effect. By 
      immunohistochemistry, D1 dopamine receptors were identified in the gerbil 
      auditory cortex predominantly in the infragranular layers. Together, these 
      findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate 
      mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours 
      or days the consolidation of memory required for the discrimination of complex 
      auditory stimuli.
FAU - Schicknick, Horst
AU  - Schicknick H
AD  - Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany.
FAU - Schott, Bjorn H
AU  - Schott BH
FAU - Budinger, Eike
AU  - Budinger E
FAU - Smalla, Karl-Heinz
AU  - Smalla KH
FAU - Riedel, Anett
AU  - Riedel A
FAU - Seidenbecher, Constanze I
AU  - Seidenbecher CI
FAU - Scheich, Henning
AU  - Scheich H
FAU - Gundelfinger, Eckart D
AU  - Gundelfinger ED
FAU - Tischmeyer, Wolfgang
AU  - Tischmeyer W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080304
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Receptors, Dopamine D1)
RN  - 67287-49-4 (2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - VTD58H1Z2X (Dopamine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology
MH  - Animals
MH  - Anisomycin/pharmacology
MH  - Auditory Cortex/*physiology
MH  - Conditioning, Psychological/drug effects/physiology
MH  - Discrimination Learning/drug effects/*physiology
MH  - Dopamine/*metabolism
MH  - Dopamine Agonists/pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Gerbillinae
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/pharmacology
MH  - Male
MH  - Memory/drug effects/*physiology
MH  - Protein Kinases/*metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Receptors, Dopamine D1/agonists/antagonists & inhibitors/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC2567422
EDAT- 2008/03/07 09:00
MHDA- 2008/12/23 09:00
PMCR- 2008/03/04
CRDT- 2008/03/07 09:00
PHST- 2008/03/07 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/03/07 09:00 [entrez]
PHST- 2008/03/04 00:00 [pmc-release]
AID - bhn026 [pii]
AID - 10.1093/cercor/bhn026 [doi]
PST - ppublish
SO  - Cereb Cortex. 2008 Nov;18(11):2646-58. doi: 10.1093/cercor/bhn026. Epub 2008 Mar 
      4.