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.

Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

“…In addition to oxytocin acting in the NTS to amplify vagally-mediated satiation signals, Wald and colleagues revealed that NTS oxytocin signaling reduces conditioned motivated behaviors for palatable food. Specifically, oxytocin administration to the NTS reduces motivation to work for sucrose in a progressive ratio schedule of operant reinforcement, and reduces reinstatement of palatable food-seeking behavior [ 47 ]. Altogether, these data indicate that NTS OT-R signaling is important for amplification of GI signals in the control of both satiation and food-motivated behavior.…”

“…Further, numerous studies have shown that central oxytocin preferentially reduces intake of and motivated responding for sweet-tasting palatable foods, in part, through actions on the VTA and ACB [ 7 , 10 , 64 , 67 , 68 ]. For example, recent evidence demonstrates that direct administration of an OT-R antagonist in the VTA significantly increases sucrose intake [ 10 ], and VTA OT-R agonism reduces sucrose motivation and chocolate pellet seeking [ 47 ]. A potential molecular mechanism through which oxytocin exerts these effects may be through modulation of dopaminergic signaling.…”

“…For example, oxytocin neurons project to various regions in the brain reward circuitry, including VTA and SNc, ACB, PFC, and extended amygdala [ 65 , 70 , 72 , 74 , 146 ]. Emerging evidence suggests that oxytocin acts directly within the mesolimbic pathway (ACB core, VTA) to inhibit food intake [ 7 , 10 , 47 ]. Further, oxytocin delivered to the cerebral ventricles, NTS, or VTA reduces motivation to work for palatable food and reduces re-instatement of food-seeking behavior [ 47 ].…”

An open-source device for measuring food intake and operant behavior in rodent home-cages

“…Has their feeding gained a compulsive nature that is insensitive to satiety signals? These questions can be answered with operant tasks, where rodents receive food contingent on their actions (Curtis et al, 2019;Mourra et al, 2020;O'Connor et al, 2015;Skinner, 1938;Thorndike, 1898;Wald et al, 2020). Typically, operant behavior is tested in dedicated chambers for a few hours each day.…”

The central nucleus of the amygdala and gustatory cortex assess affective valence during CTA learning and expression in male and female rats

“…4h The supraoptic nucleus (SON) responds to acute LiCl 43,44 . It is the primary site of oxytocin production, which is known to have emetic and anorectic properties [45][46][47][48] . The c-Fos response in the SON increased markedly in response to LiCl [F (2,16) =54.36, p< 0.001 effect of treatment], with no response to Boost® (Fig.…”