Nucleus accumbens GLP-1 receptors influence meal size and palatability

Abstract

Recent evidence suggests that the glucagon-like peptide-1 (GLP-1) neuronal projection to the nucleus accumbens core (NAcC) contributes to food intake control. To investigate the role of endogenous stimulation of GLP-1 receptors (GLP-1R) in NAcC, we examined the effects of the GLP-1R antagonist exendin-(9-39) (Ex9) on meal pattern and microstructure of ingestive behavior in rats. Intra-NAcC Ex9 treatment selectively increased meal size relative to vehicle in rats consuming 0.25 M sucrose solution or sweetened condensed milk. Microstructural analysis revealed effects of NAcC Ex9 on initial lick rate and the size and duration of licking bursts in rats consuming 0.1 or 0.25 M sucrose, suggesting that blockade of NAcC GLP-1R increases palatability. Because NAcC Ex9 did not affect licking for nonnutritive saccharin (0.1%), we suggest that the presence of nutrients in the gut may be required for endogenous stimulation of NAcC GLP-1R. Consistent with this, we also found that the meal size-suppressive effects of intragastric nutrient infusion were attenuated by NAcC delivery of Ex9 at a dose that had no effect when delivered alone. Analysis of licking patterns revealed that NAcC Ex9 did not reverse intragastric nutrient-induced suppression of burst number but rather blunted the effect of nutrient infusion on meal size primarily by increasing the size and duration of licking bursts. Together, our results suggest that NAcC Ex9 influences taste evaluation. We conclude that GLP-1 released in NAcC in response to gastrointestinal nutrients reduces the hedonic value of food.

Keywords: glucagon-like peptide-1; licking microstructure; nucleus accumbens; palatability; satiation.

Fig. 1.

Representative image of a nucleus accumbens core (NAcC) injection site (ventral aspect outlined with dotted line) in a cresyl violet-stained coronal section, and diagram based on Paxinos and Watson (17) with a box identifying the location at which the photograph was taken. AC, anterior commissure. This section is ∼1.4 mm anterior to bregma. All rats included in these studies had injection sites similar to this, in close proximity to the AC, at rostrocaudal levels ranging from 1 to 2 mm anterior to bregma.

Fig. 2.

Effects of intra-NAcC injection of vehicle or 3 μg of exendin-(9–39) (Ex9) on licking for SCM (sweetened condensed milk diluted 50:50 with water). A: size (no. of licks) of the 1st meal of the test session. B: no. of meals taken during the 120-min session. Data are means ± SE. *P < 0.05, vehicle vs. Ex9.

Fig. 3.

Effects of intra-NAcC injection of vehicle (V) or 3 μg Ex9 (E) on licking for 0.25 M sucrose. A: size (no. of licks) of the 1st 3 meals of the test session. B: duration (min) of each of the 1st 3 meals of the session. C: no. of meals taken during the session. D: Intermeal intervals (IMI) between 1st, 2nd, and 3rd meals of the session. Data are means ± SE. *P < 0.05, vehicle vs. Ex9.

Fig. 4.

Licking microstructure effects when rats were licking for 0.25 M sucrose after intra-NAcC injection of vehicle (V) or 3 μg Ex9 (E). A: meal average burst size (licks/burst) for the 1st 3 meals of the session. B: lick rate (licks/min) during the 1st meal segmented into 3rds, with data plotted at the mean temporal midpoint of each 3rd. C: burst size across 3rds of each of the 1st 3 meals of the session. Data are means ± SE. *P < 0.05, vehicle vs. Ex9.

Fig. 5.

Effects of intra-NAcC injection of vehicle (V) or 3 μg Ex9 (E) on licking for 0.1 M sucrose. A: size (no. of licks) of the 1st 2 meals of the test session. B: no. of meals taken during the session. C: IMI between 1st and s2nd meals of the session. Data are means ± SE. *P < 0.05, vehicle vs. Ex9.

Fig. 6.

Licking microstructure effects when rats were licking for 0.1 M sucrose after intra-NAcC injection of vehicle (V) or 3 μg Ex9 (E). A: no. of licks emitted during the 1st min of the 1st meal of the session. B: meal average licks/burst during the 1st and 2nd meals of the session. C: burst size across 3rds of 1st meal of the session, with data plotted at the mean temporal midpoint of each 3rd. Data are means ± SE. *P < 0.05, vehicle vs. Ex9.

Fig. 7.

Effects of intra-NAcC injection of vehicle or 2 μg Ex9 on licking for 0.25 M sucrose when receiving intragastric (IG) control (C) or sucrose (S) infusions. A: size (no. of licks) of the 1st meal of the test session. B: duration (min) of that 1st meal. C: interval between the 1st and 2nd meals of the session. D: no. of licking bursts in the 1st meal. E: average burst size during the 1st 3rd of the 1st meal (approximately the first 3.3 min). F: average duration (s) of bursts during the 1st 3rd of the 1st meal. Data are means ± SE. *P < 0.05, control vs. sucrose infusion.