Document Detail

Adaptations in the mesoaccumbens dopamine system resulting from repeated administration of dopamine D1 and D2 receptor-selective agonists: relevance to cocaine sensitization.
MedLine Citation:
PMID:  9860115     Owner:  NLM     Status:  MEDLINE    
The mesoaccumbens dopamine (DA) system is intricately involved in sensitization to the locomotor stimulant effects of cocaine. Among the adaptations implicated in cocaine sensitization are transient subsensitivity of impulse-regulating DA D2 autoreceptors on ventral tegmental area (VTA) DA neurons leading to hyperactivity of the mesoaccumbens DA pathway, and persistently enhanced DA D1 receptor responses of nucleus accumbens (NAc) neurons. We have tested the hypothesis that both of these adaptations are necessary to produce cocaine sensitization. We injected rats twice daily for 2 weeks with the selective DA D1 class receptor agonist SKF 38393, the DA D2 class receptor agonist quinpirole, or both. We then used single-cell recording procedures to determine possible alterations in VTA DA autoreceptor sensitivity and NAc D1 receptor sensitivity at three withdrawal times: 1 day, 1 week and 1 month. We also tested whether these treatments produced cross-sensitization to cocaine at each withdrawal time. Repeated quinpirole treatment produced a reduction in VTA autoreceptor sensitivity and cross-sensitization to cocaine, but these effects lasted for less than 1 week. Repeated SKF 38393 treatment produced enhanced NAc D1 responses which lasted for 1 week and cross-sensitization to cocaine which was only evident after 1 week of withdrawal. Repeated treatment with the combination of the two agonists transiently down-regulated autoreceptor sensitivity, enhanced and prolonged D1 receptor supersensitivity (lasting 1 month), and produced enduring cross-sensitization to cocaine. These results suggest that neuroadaptations within both the VTA and NAc may be necessary for the induction of enduring cocaine sensitization.
D J Henry; X T Hu; F J White
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychopharmacology     Volume:  140     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-02-25     Completed Date:  1999-02-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  233-42     Citation Subset:  IM    
Department of Cellular and Molecular Pharmacology, Finch University of Health Sciences, The Chicago Medical School, North Chicago, IL 60064-3095, USA.
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MeSH Terms
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
Autoreceptors / drug effects,  physiology
Cocaine / pharmacology*
Nucleus Accumbens / drug effects,  physiology*
Quinpirole / pharmacology
Rats, Sprague-Dawley
Receptors, Dopamine D1 / agonists,  physiology*
Receptors, Dopamine D2 / agonists,  physiology*
Ventral Tegmental Area / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Autoreceptors; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 50-36-2/Cocaine; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 85760-74-3/Quinpirole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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