Document Detail


D3 receptors and the actions of neuroleptics in the ventral striatopallidal system of schizophrenics.
MedLine Citation:
PMID:  10415673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mesolimbic dopamine (DA) system and an important target receptor, the D3 receptor, have been implicated in schizophrenia. We have identified, using non-radioactive in situ hybridization histochemistry, that D3 mRNA-positive neurons are highly concentrated in the ventral striatum, efferents of the ventral striatum (globus pallidus internal, ventral palladium, substantia nigra pars reticulata), and in regions projecting to the ventral striatum (medial dorsal thalamus, nucleus basalis, extended amygdala). D3 receptors are also highly enriched in the "limbic" striatal-pallidal-thalamic loop, exhibiting segregation from the D2 receptor-enriched "motor loop." This supports data developed in rats showing that the D3 receptor is a target of the mesolimbic DA system that can modulate the limbic striatal-palladial-thalamic loop. However, D2 and D3 receptors and their mRNAs are co-localized in many sensory regions (lateral and medial geniculate nuclei, basolateral and basomedial amygdala, regions of thalamus), suggesting mechanisms of cross-talk. We have also demonstrated that there are 45% elevations in D3 receptor number in ventral striatal neurons and their striatopalladial targets in schizophrenics that is reduced by concurrent antipsychotic treatment. Chronic haloperidol treatment to rats for 6 months with a 2-month withdrawal does not result in elevated D3 receptor number. We hypothesize that antipsychotic treatment via D3 receptors returns balance to limbic efferents of the ventral striatum. We established that early neonatal damage to the nigrostriatal DA system in rats produces characteristic adaptations in the pre- and post-synaptic components of the mesolimbic DA system that can provide a model to explore regulation by antipsychotics. This includes elevated release of DA from the mesolimbic DA terminals, elevated D3 receptor mRNA in the Islands of Calleja and nucleus accumbens, and enhanced behavioral response to psychostimulants.
Authors:
J N Joyce; E V Gurevich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  877     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-08-10     Completed Date:  1999-08-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  595-613     Citation Subset:  IM    
Affiliation:
Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona 85351, USA. jjoyce@mail.sunhealth.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Antipsychotic Agents / pharmacology,  therapeutic use*
Corpus Striatum / drug effects,  physiology,  physiopathology*
Globus Pallidus / drug effects,  physiology,  physiopathology*
Humans
RNA, Messenger / analysis
Rats
Receptors, Dopamine D2 / drug effects,  genetics,  physiology*
Receptors, Dopamine D3
Schizophrenia / drug therapy*,  physiopathology*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
AG 09215/AG/NIA NIH HHS; MH 56824/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/DRD3 protein, human; 0/Drd3 protein, rat; 0/RNA, Messenger; 0/Receptors, Dopamine D2; 0/Receptors, Dopamine D3

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