PMID- 16092936
OWN - NLM
STAT- MEDLINE
DCOM- 20050927
LR  - 20121115
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 94
IP  - 4
DP  - 2005 Aug
TI  - Serotonin 5-HT receptor blockade enhances Ca(2+)/calmodulin-dependent protein 
      kinase II function and membrane expression of AMPA receptor subunits in the rat 
      hippocampus: implications for memory formation.
PG  - 884-95
AB  - Stimulation of hippocampal 5-HT(1A) receptors impairs memory retention. The 
      highly selective 5-HT(1A) antagonist, WAY-100635, prevents the cognitive deficits 
      induced not only by 5-HT(1A) stimulation but also by cholinergic or NMDA receptor 
      blockade. On this basis, the effects of WAY-100635 on molecular events associated 
      with memory storage were explored. In rat hippocampus, WAY-100635 produced a 
      rapid increase in phosphorylated Ca(2+)/calmodulin-dependent protein kinase II 
      (CaMKII) and in Ca(2+)-independent CaMKII and protein kinase A (PKA) enzyme 
      activity. This increase was followed a few hours later by an enhanced membrane 
      expression of AMPA receptor subunits, especially of the GluR1 subunit 
      phosphorylated at the CaMKII site, pGluR1(Ser831). The same qualitative effects 
      were found with the weaker 5-HT(1A) antagonist NAN-190. The effects of both 
      antagonists were no longer apparent in rats with a previous 5-HT depletion 
      induced by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA), 
      suggesting that 5-HT(1A) receptor blockade removes the tonic inhibition of 5-HT 
      through 5-HT(1A) receptor stimulation on excitatory hippocampal neurons, with the 
      consequent increase in PKA activity. In addition, administration of WAY-100635 
      potentiated the learning-specific increase in the hippocampus of phospho-CaMKII, 
      Ca(2+)-independent CaMKII activity, as well as the phosphorylation of either the 
      CaMKII or the PKA site on the AMPA receptor GluR1 subunit. This study suggests 
      that blockade of hippocampal 5-HT(1A) receptors favours molecular events 
      critically involved in memory formation, and provides an in vivo molecular basis 
      for the proposed utility of 5-HT(1A) receptor antagonists in the treatment of 
      cognitive disorders.
FAU - Schiapparelli, Lucio
AU  - Schiapparelli L
AD  - Division of Neuroscience, Center for Applied Medical Research, School of 
      Medicine, University of Navarra, Pamplona, Spain.
FAU - Del Rio, Joaquin
AU  - Del Rio J
FAU - Frechilla, Diana
AU  - Frechilla D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Piperazines)
RN  - 0 (Protein Isoforms)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Serotonin 5-HT1 Receptor Antagonists)
RN  - 0 (Serotonin Antagonists)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Membrane/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Memory/*physiology
MH  - Phosphoprotein Phosphatases/metabolism
MH  - Piperazines/pharmacology
MH  - Protein Isoforms/metabolism
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, AMPA/*metabolism
MH  - *Serotonin 5-HT1 Receptor Antagonists
MH  - Serotonin Antagonists/pharmacology
EDAT- 2005/08/12 09:00
MHDA- 2005/09/28 09:00
CRDT- 2005/08/12 09:00
PHST- 2005/08/12 09:00 [pubmed]
PHST- 2005/09/28 09:00 [medline]
PHST- 2005/08/12 09:00 [entrez]
AID - JNC3193 [pii]
AID - 10.1111/j.1471-4159.2005.03193.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 Aug;94(4):884-95. doi: 10.1111/j.1471-4159.2005.03193.x.