Document Detail

Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine.
MedLine Citation:
PMID:  23766142     Owner:  NLM     Status:  MEDLINE    
WC 44 and WC 10 are phenylpiperazines with low (23 fold) to moderate (42 fold) selectivity for dopamine D3 receptors (D3Rs) over D2Rs, respectively. WC 44 is a full D3R agonist in the forskolin-stimulated adenylyl cyclase (AC) assay, whereas WC 10 has little efficacy. In contrast to their opposite effects in the AC assay, these drugs often produce similar behavioral effects, suggesting that the AC assay does not predict the efficacy of these drugs in vivo. Here, we examined whether Fos protein expression induced by these drugs would be more consistent with their behavioral effects in vivo. Rats received either vehicle, WC 10 (5.6 mg/kg, i.p.), WC 44 (10.0 mg/kg, i.p), cocaine (10.0 mg/kg, i.p.), or cocaine with WC 10 (5.6 mg/kg, i.p.) or with WC 44 (10.0 mg/kg, i.p). Locomotion was monitored for 90 min and the brains were harvested for immunohistochemistry. Both WC 10 and WC 44 decreased spontaneous and cocaine-induced locomotion. Both compounds also increased Fos expression relative to saline in the dorsal striatum and nucleus accumbens core and shell, and relative to cocaine alone in the nucleus accumbens shell. The findings suggest that even though these compounds have different efficacy in the AC bioassy, they produce similar brain activation and attenuation of cocaine hyperlocomotion. Together with our previous research demonstrating that these compounds down-shift the cocaine self-administration dose-effect function, the findings support the idea that D3R-selective compounds may be useful for cocaine dependence medications development.
Brian C Nolan; Shinban Liu; Lindsey R Hammerslag; Timothy H C Cheung; Jeffrey Lenz; Robert H Mach; Robert R Luedtke; Janet L Neisewander
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-07-17
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  67     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-10-16     Completed Date:  2014-03-25     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Cocaine / administration & dosage,  pharmacology*
Corpus Striatum / drug effects,  metabolism,  physiology
Drug Combinations
Locomotion / drug effects
Nucleus Accumbens / drug effects,  metabolism,  physiology
Piperazines / administration & dosage,  pharmacology*
Proto-Oncogene Proteins c-fos / genetics,  metabolism*
Rats, Sprague-Dawley
Receptors, Dopamine D3 / agonists
Grant Support
Reg. No./Substance:
0/Drug Combinations; 0/Piperazines; 0/Proto-Oncogene Proteins c-fos; 0/Receptors, Dopamine D3; 0/WC10 compound; 0/WC44 compound; I5Y540LHVR/Cocaine; J9225CBI7D/phenylpiperazine

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

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