Fig. 6: Inhibition of CeA D2R neuronal activity enhances compulsive-like eating behavior. | Molecular Psychiatry

Fig. 6: Inhibition of CeA D2R neuronal activity enhances compulsive-like eating behavior.

From: Dopamine D2 receptor modulation of insulin receptor signaling in the central amygdala: implications for compulsive-like eating behavior

Fig. 6

A Diagram of AAV-DIO-eNpHR3.0-eYFP injection into the CeA. B Experimental scheme of light/dark box test using optogenetic inhibition. Optic stimulation: 532 nm, 5 mW, continuous. C-D Basal body weight and food intake for 1 week. E-F Time spent in each box and the number of crossovers during 15-min pre-test. G Food consumption in light box during 10-min total laser-off and -on periods. Two- way ANOVA, Bonferroni post hoc tests, genotype × laser interaction: F1,20 = 18.86, p = 0.0003, **p < 0.01 vs. WT, ##p < 0.01 vs. laser-off. H Time course of food consumption in laser-off and -on 5-min periods. Green shaded-square: laser-on period. Unpaired student’s t-test, two-tailed, *p = 0.0261, **p = 0.0019. WT NC/PF n = 6, Drd2-Cre NC n = 5, PF n = 6. All values in the data represent mean ± SEM. I proposed interplay between D2Rs and InsRs in the CeA. A decrease in CeA D2R-expressing neuronal activity is associated with palatable food (PF) consumption. Activation of D2R induces InsR phosphorylation via Gi protein coupling and PTP1B inhibition as demonstrated in this study. The synergistic activation of D2Rs and InsRs enhances CeA D2R-expressing neuron activity, thereby controlling PF intake. Conversely, loss or blockade of D2Rs disrupts InsR signaling, leading to reduced CeA D2R-expressing neuron activity and increased PF consumption. Therefore, proper coordination between D2R and InsR signaling is critical for fine-tuning brain insulin sensitivity and managing normal or maladaptive eating behavior.

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