Systemic fluoro-exendin-4 crosses the blood–brain barrier, distributes to the nucleus accumbens shell, and binds putative GLP-1 receptors expressed on D1R- and D2R-expressing MSNs. Transgenic rats expressing Cre recombinase under the GAD1 promoter, Drd1a promoter, or Drd2 promoter were infused with AAV2-hSyn-DIO-mCherry into the nucleus accumbens shell. Three weeks following viral infusion, rats were pretreated with fluoro-Ex-4 (3.0 µg/kg, i.p.) and perfused 3 h later. White arrows highlight neurons colabeled with Cre recombinase (mCherry; red) and fluoro-exendin-4 (green fluorescence). DAPI-labeled cell nuclei are indicated by blue fluorescence. Fluoro-Ex-4 was internalized by D1R-expressing MSNs (b) and D2R-expressing MSNs (d) 3 h post infusion. Approximately 64.1% of D1R-expressing MSNs (c) and 67.5% of D2R-expressing MSNs (e) in the accumbens shell were bound by fluoro-Ex-4 (n = 3/group) (FLEX=fluoro-Ex-4)