Figure 1

The glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in the lateral septum (LS) where GLP-1R agonists block cocaine-induced dopamine (DA) in vivo. (a-c) Cells expressing the GLP-1R (white in a, red in c) and terminals expressing dopamine transporter (DAT; white in b, green in c) in rostral LS (GLP-1R in a, DAT in b, merge in c). Confocal images in z stack through 13 planes taken with a × 10 objective. (d-f) Cells expressing the GLP-1R (white in d, red in f) and terminals expressing DAT (white in e, green in f) in caudal LS (GLP-1R in d, DAT in e, merge in f). Confocal images in z stack through 14 planes taken with a × 10 objective. (g) DA release induced by 30 mm KCl (representative of n=3) in section from the caudal LS. Approximate site of recording is demarcated by * in f. Ld, laterodorsal tegmental nucleus; LSd, dorsal LS; LSi, intermediate LS; LSv, ventral LS; MS, medial septum; SHi, septohippocampal nucleus. Dotted lines delineate region boundaries.²⁶ Scale bars, 100 μm. (h) Representative c-fos expression in the LS 30 min following vehicle (top) or Ex-4 (30 μg kg⁻¹, intraperitoneally, bottom) injection. Dotted box includes the LS. (i) Quantification of optical density analysis of c-fos autoradiographs in LS (t(14)=3.26; **P<0.01 by Student’s t-test; n=8). (j) Cocaine (50 μm) greatly increased septal DA levels in mice pretreated with saline (intraperitoneally, solid circles). This cocaine-induced DA increase is significantly diminished in mice pretreated with Ex-4 (1 μg kg⁻¹ intraperitoneally, solid triangles; 30 μg kg⁻¹ intraperitoneally, solid squares). Extracellular concentrations of DA are expressed as the percentage of basal levels in two fractions collected before the intervention; significant analysis of variance. Open symbols indicate significance by post hoc test where P<0.001 at 150 min and P<0.05 at 120 min; n=5–6 per group.