Document Detail


Effect of amphetamine-induced dopamine release on radiotracer binding to D1 and D2 receptors in rat brain striatal slices.
MedLine Citation:
PMID:  11111836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The in vivo binding of positron emission tomography (PET) and single photon emission computer tomography (SPECT) radiotracers to dopamine D2 receptors in the striatum can be influenced by competition with endogenous dopamine. The present study was undertaken to determine if a similar inhibition of radiotracer binding to dopamine receptors could be observed following pharmacologically-evoked dopamine release in rat brain striatal slices. Striatal slices were incubated in a large volume of oxygenated Krebs saline and exposed to amphetamine or methamphetamine to evoke dopamine release within the slice. Amphetamine and methamphetamine, at concentrations up to 30 microM, reduced [3H]raclopride binding in the slices by 77% and 86%, respectively, with 50% inhibition at 1.6 microM amphetamine or 3.0 microM methamphetamine. Neither drug produced a significant effect on binding of [3H]SCH 23390 in the slices. This suggests that dopamine was able to interfere with radiotracer binding to D2 but not D1 receptors. The dopamine uptake blockers, cocaine and methylphenidate, had relatively little effect by themselves on [3H]raclopride binding but, by inhibiting amphetamine-induced dopamine release, significantly reduced inhibition of [3H]raclopride binding by a low (3 microM) amphetamine concentration. At a higher (30 microM) amphetamine concentration the inhibition of [3H]raclopride binding was not antagonized by uptake blockers and data obtained from homogenate binding experiments indicated a direct displacement of [3H]raclopride binding by amphetamine at this concentration. In conclusion the data obtained in the present study demonstrate that the effects of amphetamine on striatal radiotracer accumulation observed in PET and SPECT can also be observed in brain slices in vitro and, at least at low amphetamine concentrations, are mediated by competition with released dopamine.
Authors:
A N Gifford; M H Park; T L Kash; L M Herman; E H Park; S J Gatley; N D Volkow
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  362     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-03-01     Completed Date:  2001-03-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  413-8     Citation Subset:  IM    
Affiliation:
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gifforda@bnl.gov
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MeSH Terms
Descriptor/Qualifier:
Amphetamine / pharmacology*
Animals
Benzazepines / metabolism
Corpus Striatum / drug effects*,  metabolism
Dopamine / secretion*
Male
Methamphetamine / pharmacology
Raclopride / metabolism
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 / metabolism*
Receptors, Dopamine D2 / metabolism*
Tomography, Emission-Computed
Tomography, Emission-Computed, Single-Photon
Grant Support
ID/Acronym/Agency:
1R01DA/NS11552-01/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Benzazepines; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 300-62-9/Amphetamine; 537-46-2/Methamphetamine; 84225-95-6/Raclopride

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


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