Journal Article

Stimulation of Dopamine D4 Receptors in the Nucleus Accumbens Shell Increases Palatable Food Intake in Satiated Male Rats: Modulation by NMDA and AMPA Receptors

Florán, Benjamín, Vidal-López, Dolores Guadalupe, Escartín-Pérez, Rodrigo Erick, Cruz-Trujillo, Refugio, Mancilla-Diaz, Juan Manuel, Tejas-Juárez, Juan Gabriel, Díaz-Urbina, Daniel, Díaz-Gandarilla, José Alfredo

2024

Overview

Background/Objectives: Palatability significantly influences food consumption, often leading to overeating and obesity by activating the brain’s reward systems. The nucleus accumbens (NAc) plays a central role in this process, modulating reward mechanisms primarily via dopamine through D2-like receptors (D2R, D3R, D4R). While the involvement of D2 receptors in feeding is well-documented, the role of D4 receptors (D4Rs) is less clear. Methods: Male Wistar rats received intra-NAc shell microinjections of the D4R agonist PD-168077 and the antagonist L-745870. This study also examined the modulation between D4R and glutamatergic transmission by administration of NMDA, NMDA receptor antagonist AP-5, AMPA, and AMPA receptor antagonist CNQX. Results: PD-168077 increased sweet solution intake by 46%, an effect that was reversed by L-745870. Pre-treatment with NMDA prevented the stimulatory effect of PD-168077, whereas the NMDA receptor antagonist AP-5 had no such effect. Additionally, AMPA administration reduced sweet solution intake by 63%, counteracting the effect of PD-168077, while the AMPA receptor antagonist CNQX, on its own, increased intake by 40%. Conclusions: These findings suggest that D4Rs promote hedonic feeding by modulating glutamatergic transmission in the NAc shell, highlighting the complexity of D4R involvement in food intake regulation. This study underscores the potential of targeting D4Rs for therapeutic interventions in eating disorders and obesity, though further research is essential to clarify the precise mechanisms through which D4R modulates AMPA and NMDA receptor activity in feeding behavior.

• Publisher: MDPI AG,MDPI
• Subject: AMPA receptor / Brain research / Carbohydrates / Cardiac glycosides / Cardiotonic agents / Diet / Dopamine / Dopamine D2 receptors / Dopamine D3 receptors / dopamine D4 receptor / Dopamine D4 receptors / Dopamine receptors / Drugs / Eating disorders / Ethics / Feeding behavior / Food / Food consumption / Food intake / Glutamatergic transmission / Glutamic acid receptors (ionotropic) / Hypothalamus / Laboratory animals / Medical research / Medicine, Experimental / N-Methyl-D-aspartic acid receptors / NMDA receptor / Nucleus accumbens / nucleus accumbens shell / Obesity / Palatability / Phenols / Proteins / Reinforcement / Sucrose / Surgery / Taste / Therapeutic applications / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors