NTS and VTA oxytocin reduces food motivation and food seeking

Abstract

Oxytocin (OT) is a neuropeptide whose central receptor-mediated actions include reducing food intake. One mechanism of its behavioral action is the amplification of the feeding inhibitory effects of gastrointestinal (GI) satiation signals processed by hindbrain neurons. OT treatment also reduces carbohydrate intake in humans and rodents, and correspondingly, deficits in central OT receptor (OT-R) signaling increase sucrose self-administration. This suggests that additional processes contribute to central OT effects on feeding. This study investigated the hypothesis that central OT reduces food intake by decreasing food seeking and food motivation. As central OT-Rs are expressed widely, a related focus was to assess the role of one or more OT-R-expressing nuclei in food motivation and food-seeking behavior. OT was delivered to the lateral ventricle (LV), nucleus tractus solitarius (NTS), or ventral tegmental area (VTA), and a progressive ratio (PR) schedule of operant reinforcement and an operant reinstatement paradigm were used to measure motivated feeding behavior and food-seeking behavior, respectively. OT delivered to the LV, NTS, or VTA reduced 1) motivation to work for food and 2) reinstatement of food-seeking behavior. Results provide a novel and additional interpretation for central OT-driven food intake inhibition to include the reduction of food motivation and food seeking.

Keywords: appetitive behavior; hindbrain; midbrain; motivated behavior; oxytocin receptor.

Fig. 1.

Representative photomicrograph and schematic depicting injection sites in the NTS. The white arrow designates an injection site. Coordinates are relative to the bregma. NTS, nucleus tractus solitaries. Brain maps are derived from Swanson (64a).

Fig. 2.

Representative photomicrograph and schematic depicting injection sites in the VTA. The white arrow designates an injection site. Coordinates are relative to the bregma. VTA, ventral tegmental area. Brain maps are derived from Swanson (64a).

Fig. 3.

LV OT reduces food intake, food motivation, and food-seeking behavior. LV OT reduced chow intake (A) and reduced active-lever presses (B) and pellets earned (C) under a progressive ratio schedule of reinforcement. Pellet plus cue priming increased active-lever presses during reinstatement testing (D), which was reduced by LV OT delivery (E). LV, lateral ventricle; OT, oxytocin. *P < 0.05 and error bars represent SE.

Fig. 4.

NTS OT delivery reduces food intake, food motivation, and food seeking. NTS OT delivery reduced chow intake (A). NTS OT reduced active-lever presses and pellets earned in a progressive ratio schedule of reinforcement with 0.25 µg OT (B and C) and active-lever presses and pellets earned under a progressive ratio schedule of reinforcement with 1 µg OT (D and E). Pellet plus cue priming increased active-lever presses during reinstatement testing (F), which was reduced by NTS OT delivery (G). *P < 0.05 and error bars represent SE. NTS, nucleus tractus solitaries; OT, oxytocin.

Fig. 5.

VTA OT delivery reduced food intake, food motivation, and food seeking. VTA OT delivery reduced chow intake (A) and active-lever presses (B) and pellets earned (C) in a progressive ratio schedule of reinforcement. Pellet plus cue priming increased active-lever presses during reinstatement testing (D), which was reduced by VTA OT delivery (E). *P < 0.05 and error bars represent SE. VTA, ventral tegmental area; OT, oxytocin.