Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity

Abstract

Increased caloric intake in dietary obesity could be driven by central mechanisms that regulate reward-seeking behavior. The mesolimbic dopamine system, and the nucleus accumbens in particular, underlies both food and drug reward. We investigated whether rat dietary obesity is linked to changes in dopaminergic neurotransmission in that region. Sprague-Dawley rats were placed on a cafeteria-style diet to induce obesity or a laboratory chow diet to maintain normal weight gain. Extracellular dopamine levels were measured by in vivo microdialysis. Electrically evoked dopamine release was measured ex vivo in coronal slices of the nucleus accumbens and the dorsal striatum using real-time carbon fiber amperometry. Over 15 weeks, cafeteria-diet fed rats became obese (>20% increase in body weight) and exhibited lower extracellular accumbens dopamine levels than normal weight rats (0.007±0.001 vs. 0.023±0.002 pmol/sample; P<0.05). Dopamine release in the nucleus accumbens of obese rats was stimulated by a cafeteria-diet challenge, but it remained unresponsive to a laboratory chow meal. Administration of d-amphetamine (1.5 mg/kg i.p.) also revealed an attenuated dopamine response in obese rats. Experiments measuring electrically evoked dopamine signal ex vivo in nucleus accumbens slices showed a much weaker response in obese animals (12 vs. 25 × 10 6 dopamine molecules per stimulation, P<0.05). The results demonstrate that deficits in mesolimbic dopamine neurotransmission are linked to dietary obesity. Depressed dopamine release may lead obese animals to compensate by eating palatable "comfort" food, a stimulus that released dopamine when laboratory chow failed.Keywords nucleus accumbens; striatum; feeding; body weight; amphetamine; hyperphagia The rapid rise of dietary obesity in industrialized societies indicates that non-homeostatic signaling pathways that allow for chronic positive energy intake may be responsible. A crucial question is why laboratory animals and humans keep on eating energy-rich, palatable food to the degree that they become obese. From an evolutionary perspective, it is to be expected that the brain developed a system to respond to natural rewards, such as food. These central mechanisms are conserved across species in order to ensure survival (Kelley and Berridge,

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

“…Although debate still exists whether this can be Seeman, 2012;Skinbjerg et al, 2012), in theory, only agonist tracers like [ 11 C](+)PHNO would prefer these sites as D 2/3 R antagonist tracers typically bind with equal preference to both high-and low-affinity forms of the D 2/3 R. Therefore, it is possible that these differential binding characteristics could also help explain our VST findings such that the regulation of 'active' highaffinity forms vs 'inactive' low-affinity forms of the D 2/3 R may be altered in obesity. Our finding in the VST is also consistent with the previous [ 11 C](+)PHNO work in non-OB individuals (Caravaggio et al, 2013) and preclinical research that posits the nucleus accumbens, a central component of the VST, plays a key role in the formation/development of the OB phenotype (Davis et al, 2008;Geiger et al, 2009;Hryhorczuk et al, 2016;Rada et al, 2010;Valenza et al, 2015). This regional specificity, along with tracer properties, may help explain why differences were not found in the dorsal striatum.…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…In addition to the many effects high-fat diet has on muscles, it has also been shown to stimulate certain brain areas (for example, hypothalamus) and signaling by certain neurotransmitters (for example, dopamine), putatively involved in reward 5,[48][49][50][51] and possibly involved with the 'activitystat'. 52 Voluntary wheel running is also well known for its impact on the central nervous system, and is considered to be a classic self-rewarding behavior.…”

“…3 Diet is a highly variable environmental factor (although behavior and physiology affect dietary choices), and elucidating the role that dietary macronutrients have in providing energy during locomotion and other physiological processes should shed light on the current human obesity epidemic. 4,5 Furthermore, comparative, ecological and evolutionary physiologists are attempting to reveal how dietary physiology may interact with, and even constrain, behavioral ecology and evolution. 2,6,7 In this study, we investigated genotype-by-environmental interactions and potential limitations that diet places on locomotor behavior through the use of an artificial selection experiment using laboratory house mice.…”

High-fat diet alters the dopamine and opioid systems: effects across development

“…59 Finally, consumption of a high-fat cafeteria diet was shown to lower both basal levels of DA and DA release in response to food or amphetamine. 60 In addition to DA, opioids and the MOR in particular are important in reward of palatable foods. 61,62 Through the work in our laboratory, we were the first to show that consumption of a high-fat diet could downregulate the expression of the MOR within reward circuitry structures.…”