Linked Life Data

21113004

Source:http://linkedlifedata.com/resource/pubmed/id/21113004

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 24
pubmed:dateCreated
2010-11-29
pubmed:abstractText
Pre-pulse inhibition (PPI) of the acoustic startle reflex is deficient in patients with schizophrenia. This deficiency is mimicked in mice by the use of the psychotomimetic drugs d-amphetamine and dizolcipine. Antipsychotic drugs such as clozapine are used to treat schizophrenic patients and are also administered to mice to prevent PPI disruption. Neurotensin (NT) produces antipsychotic-like effects when injected into rodent brain through its effects at NT subtype 1 (NTS1) and 2 (NTS2) receptors. We hypothesized that the NT receptor agonist (NT69L) would prevent PPI disruption in mice challenged with d-amphetamine (10 mg kg(-1)) and dizocilpine (1 mg kg(-1)). We investigated the role of NTS1 and NTS2 in PPI using wild-type (WT), NTS1 (NTS1(-/-)) and NTS2 (NTS2(-/-)) knockout mice, via its disruption by psychotomimetic drugs, as well as the ability of clozapine and NT69L to block these PPI disruptions. There were no differences in baseline PPI across the three genotypes. d-Amphetamine and dizocilpine disrupted PPI in WT and NTS2(-/-) mice but not in NTS1(-/-) mice. In WT mice, clozapine (1 mg kg(-1)) and NT69L (1 mg kg(-1)) significantly blocked d-amphetamine-induced disruption of PPI. Similarly, in WT mice, clozapine significantly blocked dizocilpine-induced PPI disruption, but NT69L did not. In NTS2(-/-) mice clozapine blocked d-amphetamine-but not dizocilpine-induced PPI disruption, while NT69L blocked both d-amphetamine- and dizocilpine-induced PPI disruption. Our results indicate that NTS1 seems essential for d-amphetamine and dizocilpine disruption of PPI. Additionally, this report provides support to the hypothesis that NT analogs could be used as novel antipsychotic drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1477-9145
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4232-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Sensorimotor gating in NTS1 and NTS2 null mice: effects of d-amphetamine, dizocilpine, clozapine and NT69L.
pubmed:affiliation
Neuropsychopharmacology Laboratory, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural