Fig. 3
The suppressive effects of systemic fluoro-exendin-4 on cocaine seeking were blocked by antagonism of VTA GLP-1 receptors. Rats pretreated with fluoro-Ex-4 (3.0 µg/kg, n = 10) prior to a priming injection of cocaine in Fig. 1a were perfused immediately after the reinstatement test session (3 h post fluoro-Ex-4 infusion). Coronal sections at the level of the midbrain a were used to determine whether systemic fluoro-Ex-4 penetrates the brain and localizes in the VTA. b 3.0 µg/kg fluoro-Ex-4 (green fluorescence) co-localized with neurons labeled with NeuN (blue fluorescence) and astrocytes labeled with GFAP (red fluorescence) in the VTA. c 3.0 µg/kg fluoro-Ex-4 co-localized with tyrosine hydroxylase-labeled dopamine neurons (red fluorescence) in the VTA. The VTA d of separate rats treated with 0.2 µg/kg fluoro-Ex-4 were used to determine if lower doses of the GLP-1 receptor agonist that selectively attenuated cocaine seeking also penetrated the brain and localized in the VTA e & f. Images are compressed z-stacks with a 0.5 µm step size (scale bar: 20 µm). All images shown at 63 × magnification. g Intra-VTA infusions of the GLP-1 receptor antagonist exendin-(9–39) (10 µg) prior to a systemic injection of 3.0 µg/kg fluoro-Ex-4 blocked fluoro-Ex-4-mediated reductions in total active lever responses during cocaine reinstatement test sessions (n = 13/treatment). h Representative coronal sections at the level of the midbrain depict microinjection sites in the VTA. *p < 0.05, Bonferroni
