Linked Life Data

7895059

Source:http://linkedlifedata.com/resource/pubmed/id/7895059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-4-25
pubmed:abstractText
Neurotensin (NT) has been proposed to be an endogenous neuroleptic based on observations that i.c.v. administration of this peptide antagonizes dopamine-mediated behavior. Because NT influences dopamine activity, this peptide may contribute to the pathogenesis of psychotic disorders such as schizophrenia; however, the precise physiological effects of NT remain speculative. In order to elucidate the function of endogenous NT, a selective NT antiserum (NTAS) was administered i.c.v. through a push-pull cannula in unanesthetized, freely moving rats in combination with dopamine activation caused by methamphetamine (METH). Locomotor and rearing activities induced by a low dose of METH (0.5 mg/kg) were substantially enhanced (4-5-fold) in rats receiving NTAS compared to control animals receiving METH alone. Similarly raised antiserum to vasoactive intestinal polypeptide (VIP) did not alter METH-induced effects. To determine a possible mechanism for these observations, perfusate delivered into the cerebral ventricular space was collected by push-pull cannulae and assayed for dopamine release. METH-induced dopamine release was enhanced 4-5-fold by co-administration of NTAS but not VIP antiserum. To verify these observations, and to identify the site of dopamine release, this experiment was repeated utilizing microdialysis and the recently described NT antagonist, SR-48692. Results from this experiment were similar to those found using NTAS. Like NTAS, co-administration of the NT antagonist enhanced the behavioral responses to a low dose of METH. These studies with SR-48692 also revealed that blockade of NT receptors increased METH-induced release of dopamine from the nucleus accumbens. These findings are the first to demonstrate directly that endogenous NT antagonizes stimulated dopamine pathways and its inactivation substantially enhances METH-induced DA release and related behaviors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
665
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
237-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Endogenous neurotensin antagonizes methamphetamine-enhanced dopaminergic activity.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.