Linked Life Data

3081693

Source:http://linkedlifedata.com/resource/pubmed/id/3081693

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1986-4-11
pubmed:abstractText
An anomaly in the experimental data underlying the theory that neuroleptics act by blockade of dopaminergic neurotransmission is the repeatedly demonstrated failure in several laboratories of parenterally administered neuroleptics to antagonize electrophysiologic actions of locally applied dopamine (DA) in striatum. This failure is enigmatic since many investigators have successfully demonstrated antagonism when both dopamine and neuroleptic are applied directly to striatal neurons by microiontophoresis. We used multibarrel micropipettes to pressure-eject DA agonists onto rat caudate neurons while observing the ability of parenterally administered haloperidol to block the inhibitory actions of dopaminergic agonists on neuronal activity. Experiments performed at times of maximal behavioural effect of haloperidol did not demonstrate agonist-antagonist interaction. This result has been obtained by four other teams of investigators. A variety of pharmacologic manipulations were employed to help solve this enigma. Acute treatment with reserpine and alpha-methyl-paratyrosine, performed to minimize any possible interference by endogenous DA, did not permit blockade of dopamine by haloperidol. To see if this failure of antagonism could be generalized to other DA agonists, apomorphine, amphetamine, and phencyclidine (PCP) were also investigated. Although the direct dopaminergic agonist apomorphine was not antagonized by haloperidol, the indirect DA agonist PCP was successfully antagonized. Amphetamine, which has both direct and indirect actions when applied locally, was not antagonized. Antagonism of direct agonists was demonstrated in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. In these preparations, parenterally administered haloperidol reversed the receptor-mediated supersensitivity to the inhibitory effects of locally applied DA and apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
572-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Investigation of the failure of parenterally administered haloperidol to antagonize dopamine released from micropipettes in the caudate.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.