Effects of Ventral Pallidum–Nucleus Accumbens Shell Neural Pathway Modulation on Sucrose Consumption and Motivation in Female Rats: Chemogenetic Manipulation

Background The neural control of food intake involves interactions between homeostatic and nonhomeostatic systems. The nucleus accumbens shell (AcbSh) and ventral pallidum (VP) play key roles in regulating ingestive behavior and project to each other. Previous studies have shown that these projections influence food consumption, with sex differences reported in the modulation of sucrose intake by VP projections. Objective This study aimed to investigate the effects of chemogenetic activation or inhibition of projections from the VP to the AcbSh on sucrose consumption and the motivation to work for sucrose in female rats. Methods Chemogenetic tools (DREADD [designer receptors exclusively activated by designer drugs]) were used to selectively activate or inhibit VP projections to the AcbSh in female Sprague-Dawley rats (Gi [inhibitory G protein] DREADD: n=11; Gq [excitatory G protein] DREADD: n=10; and no DREADD: n=12). Rats were trained on a progressive ratio operant task to assess motivation to work for sucrose. Additionally, free-access sucrose consumption tests were conducted using a 20% sucrose solution. The effects of chemogenetic modulation were analyzed using two-way ANOVA. Results Chemogenetic manipulation of VP projections to the AcbSh did not significantly affect the motivation to work for sucrose in the progressive ratio task (F2,31=1.780; P=.18). However, a significant interaction between DREADD type and drug administration was observed in the sucrose consumption test. Activation of the VP-AcbSh projection (using Gq DREADD) decreased sucrose intake, while inhibition (using Gi DREADD) increased sucrose intake (F2,31=18.891; P=.001). No significant changes in sucrose consumption were observed in the control group without DREADD expression (P=.50). Conclusions This study shows that projections from the VP to the AcbSh modulate sucrose intake but do not affect the motivation to work for sucrose. Chemogenetic activation reduced sucrose consumption, while inhibition increased it, suggesting that distinct neural circuits within the VP-AcbSh pathway may differentially regulate feeding behaviors. These findings highlight the role of this pathway in the consumption of palatable foods and indicate that future research should consider factors such as sex, food macronutrient composition, and specific neural subpopulations to better understand their role in feeding behavior.