Linked Life Data

19660530

Source:http://linkedlifedata.com/resource/pubmed/id/19660530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-10-14
pubmed:abstractText
The 5-HT(6) receptor is predominantly expressed in the CNS and has been implicated in the regulation of cognitive function. Antagonists of the 5-HT(6) receptor improve cognitive performance in a number of preclinical models and have recently been found to be effective in Alzheimer's disease patients. Systemic administration of 5-HT(6) antagonists increases the release of acetylcholine and glutamate in the frontal cortex and dorsal hippocampus. In contrast, the selective 5-HT(6) agonist, WAY-181187, can elicit robust increases in extracellular levels of GABA. The reported behavioral and neurochemical effects of 5-HT(6) receptor ligands raise the possibility that the 5-HT(6) receptor may modulate synaptic plasticity in the hippocampus. In the present study, selective pharmacological tools were employed to determine the effect of 5-HT(6) receptor activation on long-term potentiation (LTP) in brain slices containing area CA1 of the hippocampus. While having no effect on baseline synaptic transmission, the results demonstrate that the selective 5-HT(6) agonist, WAY-181187, attenuated LTP over a narrow dose range (100-300 nM). The increase in the slope of the field excitatory post synaptic potential (fEPSP) caused by theta burst stimulation in brain slices treated with the most efficacious dose of WAY-181187 (200 nM) was 80.1+/-4.0% of that observed in controls. This effect was dose-dependently blocked by the selective 5-HT(6) antagonist, SB-399885. WAY-181187 also increased the frequency of spontaneous GABA release in area CA1. As assessed by measuring and evaluating spontaneous inhibitory postsynaptic currents (sIPSCs), 200 nM WAY-181187 increased sIPSC frequency by 3.4+/-0.9 Hz. This increase in GABA sIPSCs was prevented by the selective 5-HT(6) antagonist SB-399885 (300 nM). Taken together, these results suggest that the 5-HT(6) receptor plays a role in the modulation of synaptic plasticity in hippocampal area CA1 and that the regulation of GABAergic interneuron activity may underlie the cognition enhancing effects of 5-HT(6) antagonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-7544
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
692-701
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19660530-Animals, pubmed-meshheading:19660530-CA1 Region, Hippocampal, pubmed-meshheading:19660530-Dose-Response Relationship, Drug, pubmed-meshheading:19660530-Excitatory Postsynaptic Potentials, pubmed-meshheading:19660530-Inhibitory Postsynaptic Potentials, pubmed-meshheading:19660530-Long-Term Potentiation, pubmed-meshheading:19660530-Male, pubmed-meshheading:19660530-Piperazines, pubmed-meshheading:19660530-Pyramidal Cells, pubmed-meshheading:19660530-Rats, pubmed-meshheading:19660530-Rats, Sprague-Dawley, pubmed-meshheading:19660530-Receptors, Serotonin, pubmed-meshheading:19660530-Serotonin Antagonists, pubmed-meshheading:19660530-Serotonin Receptor Agonists, pubmed-meshheading:19660530-Sulfonamides, pubmed-meshheading:19660530-Synaptic Transmission, pubmed-meshheading:19660530-Theta Rhythm, pubmed-meshheading:19660530-Thiazoles, pubmed-meshheading:19660530-Tryptamines, pubmed-meshheading:19660530-gamma-Aminobutyric Acid
pubmed:year
2009
pubmed:articleTitle
Activation of the 5-HT(6) receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus.
pubmed:affiliation
Worldwide Discovery Research, Cephalon, Inc., West Chester, PA 19380, USA. pwest@cephalon.com
pubmed:publicationType
Journal Article, In Vitro