Obese OLETF rats exhibit increased operant performance for palatable sucrose solutions and differential sensitivity to D2 receptor antagonism

Abstract

Hajnal A, Acharya NK, Grigson PS, Covasa M, Twining RC. Obese OLETF rats exhibit increased operant performance for palatable sucrose solutions and differential sensitivity to D2 receptor antagonism. Am J Physiol Regul Integr Comp Physiol 293: R1846-R1854, 2007. First published September 5, 2007; doi:10.1152/ajpregu.00461.2007.-CCK-1-receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and exhibit a greater preference for sucrose compared with lean controls [Long-Evans Tokushima Otsuka (LETO)]. To directly assess motivation to work for sucrose reward in this model of obesity and type 2 diabetes, we examined the operant performance of OLETF rats at nondiabetic and prediabetic stages (14 and 24 wk of age, respectively) on fixed-ratio (FR) and progressiveratio (PR) schedules of reinforcement. To evaluate the involvement of dopamine systems, the effects of the D1 receptor antagonist SCH23390 (100 and 200 nmol/kg ip) and the D2 receptor antagonist raclopride (200 and 400 nmol/kg ip), were also tested on PR responding for sucrose. Compared with age-matched LETO rats, 14-wk-old OLETF rats emitted more licks on the "active" empty spout operant on the FR-10 schedule of reinforcement to obtain 0.01 M and 0.3 M sucrose and completed higher ratio requirements on the PR schedule to gain access to 0.3 M and 1.0 M sucrose. At 24 wk, this effect was limited to 1.0 M sucrose. Both antagonists were potent in reducing operant responding to 0.3 M sucrose in both strains at both ages, and there was no strain effect to SCH23390 at either age. OLETF rats, on the other hand, showed an increased sensitivity to the higher dose of raclopride, resulting in reduced responding to sucrose reinforcement at 24 wk. Taken together, these findings provide the first direct evidence for an increased motivation for sucrose reward in the OLETF rats and suggest altered D2 receptor regulation with the progression of obesity and prediabetes. dietary obesity; food reward; appetite; palatability; operant lick task THE EPIDEMIC OF OBESITY AND its associated health consequences represent a major cause of preventable morbidity and mortality in the United States and worldwide (31). Although the etiology of obesity is complex, the motivation to respond to palatable food correlates with obesity (3, 52, 60). Despite this relationship, little is known about food reward functions in the obese. The common view is that obese individuals are presumed to show enhanced liking for palatable foods. Several human studies investigating the relationship between preference and obesity support this notion, whereas others debate it (3,19,20,38).Due to the complexity of human eating behavior there has been growing interest in using animal models to decipher basic neural processes underlying the development of obesity. Our laboratory has been investigating the Otsuka Long-Evans Tokushima fatty (OLETF) rats that lack the CCK-1 receptor, are hyperphagic, obese, and gradually develop non-insulin-dependent diabetes mellitus (36). Unlike in other geneticall...

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

“…Dopamine signaling would then not constitute reward by itself; it would be more like a sensing mechanism leading to reward generation, just like nutrient-sensing mechanisms lead to satiation. A limitation of our study is that we have not investigated the status of dopamine signaling in rats displaying the different reward behaviors, and we can only assume that there was suppressed dopamine signaling in the obese state as reported by others (22,30,32,33,36,39,72).…”

“…As to the potential neural pathways and circuits responsible for these obesity-induced effects on food reward behaviors, there is considerable evidence for obesity-associated decreased signaling through the mesolimbic dopamine/D2-receptor system in both rodents (22,30,32,33,36,39,72) and humans (18,21,65,67,75,77). This system is thought to play a pivotal role in both the motivational ("wanting") and reinforcement learning component of food and drug reward (4, 79), and both hyperfunctioning and hypofunctioning of this system have been suggested to increase the risk of obesity.…”

“…A considerable body of literature exists demonstrating differences in reward behaviors and neural reward functions between lean and obese animals and humans (1,21,22,33,36,56,60,66; see Refs. 6,8,24,46,61, and 67 for reviews).…”

“…For the same perceived sweetness, "liking" increases as body mass index increases (2). Obese rats lacking a functional CCK-1 receptor show a rightward shift in the concentration-responses to oral sucrose and exhibit increased operant performance for high, but not low, concentrations of sucrose solutions compared with their lean counterparts (36). A similar rightward shift in the concentrationresponse to sucrose and corn oil was observed in high-fat diet-induced obese rats subjected to sham surgery, compared with rats that lost all excess body weight after Roux-en-Y gastric bypass surgery and chow-fed lean rats (60).…”

Reduced Sensitivity to Cholecystokinin in Male Rats Fed a High-Fat Diet Is Reversible

“…Thus, differences in oral oil detection by HF rats may be associated with changes in CCK signaling within the taste bud. Furthermore, perturbations in dopamine signaling have been shown to contribute to increased preference and acceptance of palatable foods, including oils (57,58). Therefore, it is plausible that the alteration in preference function and reward sensitivity at least in part is due to a maladaptive feedback mechanism that develops in response to sustained overconsumption of HF diets.…”