title: Acute binge pattern cocaine administration induces region-specific effects in D1-r- and D2-r-expressing cells in eGFP transgenic mice.
abstract: Cocaine addiction is driven by genetic, neurologic and environmental components. The D1-like (D1 and D5) and D2-like (D2, D3 and D4) families of dopamine receptors play an important role in modulating the effects of cocaine administration on drug-seeking behavior. The advent of bacterial artificial chromosome-eGFP (enhanced green fluorescent protein) transgenic mice that express eGFP driven by the endogenous D1-receptor (D1-r) or D2-receptor (D2-r) promoters provides a unique opportunity to distinguish between these subpopulations of cells. In an effort to identify cocaine-induced alterations in D1-r- versus D2-r-expressing cells during the initial stages of addiction, we examined cells that expressed D1-rs in Drd1-eGFP mice, or D2-rs in Drd2-eGFP mice, after an acute, 1-day binge pattern of cocaine administration. We used multiphoton confocal microscopy and Visiopharm© software, to conduct unbiased stereological counts of D1-r-labeled or D2-r-labeled cells in various striatal regions. Mice were sacrificed at 30 min and 24-h post cocaine or saline administration. Compared to saline controls, Drd1-eGFP mice that received cocaine had a higher count of D1-r-labeled cells in the dorsolateral (DL) striatum, at the 30-min and 24-h time-points. No changes in the nucleus accumbens (NAc) core or shell were observed in Drd1-eGFP mice. Drd2-eGFP mice that received cocaine had fewer D2-r-labeled cells in the DL striatum and NAc core compared to saline controls. This effect was observed at the 30-min time-point but not at 24h. Drd2-eGFP mice that received cocaine also had fewer numbers of D2-r-labeled cells in the NAc core compared to saline controls, but no significant differences in the number of D2-r-labeled cells in the NAc shell. These results suggest that acute binge pattern cocaine administration may induce region-specific alterations in D1-r or D2-receptor gene expression, and may help elucidate the differential role of dopamine receptors in the initial stages of the addiction cycle.
authors.affiliation: The Rockefeller University, The Laboratory of the Biology of Addictive Diseases, 1230 York Avenue, New York, NY 10065, United States. Electronic address: clawhorn@rockefeller.edu.
authors.forename: C
authors.initials: C
authors.lastname: Lawhorn
authors.forename: E
authors.initials: E
authors.lastname: Edusei
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Ho
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000473:pathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D003042:Cocaine
keywords: ANOVA; BAC; D1-r; D1-receptor; D2-r; D2-receptor; DL; MSN; NAc; PFA; SN; addiction; analysis of variance; bacterial artificial chromosome; cocaine; dopamine; dorsolateral; eGFP; enhanced green fluorescent protein; medium spiny neuron; nucleus accumbens; paraformaldehyde; stereology; striatum; substantia nigra