ACUTE BINGE PATTERN COCAINE ADMINISTRATION INDUCES REGION-SPECIFIC EFFECTS IN D1-R- AND D2-R-EXPRESSING CELLS IN EGFP TRANSGENIC MICE

作者：Lawhorn C^*; Edusei E; Zhou Y; Ho A; Kreek M J

来源：Neuroscience, 2013, 253: 123-131.

DOI：10.1016/j.neuroscience.2013.08.032

• cocaine
• addiction
• dopamine
• eGFP
• stereology
• striatum

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 (c) 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 Drdi-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 24 h. 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.

• 出版日期2013-12-3