Deep Brain Stimulation Reveals a Dissociation of Consummatory and Motivated Behaviour in the Medial and Lateral Nucleus Accumbens Shell of the Rat

Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa

Effect of DBS on the consumption of food.

<p>The graph represents mean food intake in grams (+SEM) (y-axis). Intensity of stimulation is depicted on the x-axis. Stimulation of the core (top graph) or lShell (middle) did not affect food intake. Stimulation of the mShell (bottom) at the highest intensity (100 µA) significantly increased food intake. Stimulation at lower intensities did not affect food consumption in any target area.</p

Effect of DBS on sucrose preference.

<p>The graph represents mean preference ratio's (±SEM) for all target groups (core, lshell, mshell) (y-axis). Stimulation-intensities are depicted on the x-axis. Base-line preference was significantly different from chance-levels (50% indicated by dotted-line), but was not affected by stimulation, for any group.</p

Effect of DBS on operant responding for sucrose.

<p>The graph represents the mean number of obtained rewards (+SEM) as a percentage of those obtained during sham stimulation (y-axis). Stimulation areas are depicted on the x-axis. Stimulation of the NAcc (core, lShell or mShell) did not significantly affect responding for sucrose (top) but there was a strong trend towards a significant increase in lShell stimulated animals. Responding under a progressive ratio schedule for sucrose (bottom) was not affected by DBS of the core or mShell. Stimulation of the lShell at the highest intensity (100 µA) significantly decreased responding. Stimulation at lower intensities did not affect performance in either task, in any target area.</p

Localization of the electrode-tips of all animals.

<p>The plus symbols indicate endpoints of electrodes placed in the NAcc core, closed circles indicate endpoints of electrodes placed in the lateral shell, and open circles indicate endpoints of electrodes placed in the medial shell. Animals with electrodes placed outside the target area were not included in the analysis (adapted from; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033455#pone.0033455-Paxinos1" target="_blank">[33]</a>).</p

Average number of lever presses per condition.

<p>The average (with SEM in parentheses) number of active- and inactive lever presses per condition with base-line values for each stimulation intensity. FR 1, Fixed ratio 1, PR, progressive ratio.</p