Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa

Abstract

Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of restricted eating coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. This article is part of a Special Issue entitled 'Central Control of Food Intake'.

Figure 1

Dopamine (blue), serotonin (green), acetylcholine (red) and the opioids (orange) have each been indicated in disordered eating. This schematic illustrates some of the neuronal projections that research indicates are of particular interest in the regulation and deregulation of food intake as revealed through preclinical and clinical studies of eating disorders.

Figure 2

Accumbens DA and ACh release when rats binge on sucrose at a normal body weight and then again at a reduced body weight (85% body weight). The control group had access to sucrose twice (day 1 and 21), and was similarly reduced in body weight. (A) DA is released in response to drinking 10% sucrose on day 21 of access at a normal body weight, and (B) this release is enhanced (to 179% of baseline) when animals binge on sucrose at a reduced body weight. Rats with access to sucrose only two times do not show this effect. (C) ACh rises as the sucrose meal progresses for both groups when at normal body weight. (D) This effect on ACh release is blunted for the sucrose bingeing group when at a reduced body weight. * P<0.05 from baseline. Figure reprinted with permission from (Avena et al., 2008c).

Figure 3

Changes in extracellular DA and ACh release in the NAc when rats are bingeing and purging via sham feeding. (A) DA release is increased in bingeing rats when both real-feeding and sham-feeding. Significant differences between groups are indicated by asterisks (P<0.05). Significant differences from baseline are indicated by ‡ (P<0.05). (B) ACh increased for real-feeding rats during sugar intake, but there was no response for sham-feeding rats during this time marked by black rectangles along the ordinate. Asterisks indicate that the ACh levels were significantly higher for the real- compared with sham-feeding rats. Differences from baseline for the real-feeding rats are indicated by ‡ (P<0.05). Figure reprinted with permission from (Avena et al., 2006b).