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Chunk #11 — Dopamine Receptor Signaling in D1 vs. D2 MSNs

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The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons.
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Finally, it has been reported recently that D2-GFP homozygote BAC transgenic mice display increased expression levels of the D2-receptor in striatum and enhanced behavioral sensitivity and dopamine signaling to D2 agonists. Moreover, both homozygotes and hemizygotes exhibit blunted behavioral responses to cocaine (Kramer et al., 2011). This study highlights the need to perform thorough characterization of D1 and D2 fluorescent reporter and Cre driver lines. However, the majority of the data collected in this study used homozygotes, which is not the ideal experimental genotype since 5–10% of transgene integrations result in insertional mutations (Meisler, 1992); therefore, the hemizygote genotype is the more reliable experimental genotype. Additionally, this study did not use littermate wildtype controls but used controls on a similar background (Swiss Webster) obtained from Taconic, while their transgenic lines were obtained from GENSAT and MMRRC. Finally, another group has shown normal cocaine locomotor behavioral responses in D2-GFP hemizygotes (Kim et al., 2011). Thus, future studies using proper controls and proper genotypes must be performed to fully characterize the various cell-type-specific transgenic lines available.