Enkephalin Surges in Dorsal Neostriatum as a Signal to Eat

Compulsive overconsumption of reward characterizes disorders ranging from binge eating to drug addiction. Here, we provide evidence that enkephalin surges in an anteromedial quadrant of dorsal neostriatum contribute to generating intense consumption of palatable food. In ventral striatum, mu opioid circuitry contributes an important component of motivation to consume reward [1-4]. In dorsal neostriatum, mu opioid receptors are concentrated within striosomes that receive inputs from limbic regions of prefrontal cortex [5-13]. We employed advanced opioid microdialysis techniques that allow detection of extracellular enkephalin levels. Endogenous >150% enkephalin surges in anterior dorsomedial neostriatum were triggered as rats began to consume palatable chocolates. In contrast, dynorphin levels remained unchanged. Furthermore, a causal role for mu opioid stimulation in overconsumption was demonstrated by observations that microinjection in the same anterior dorsomedial quadrant of a mu receptor agonist ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin; DAMGO) generated intense >250% increases in intake of palatable sweet food (without altering hedonic impact of sweet tastes). Mapping by Fos plume methods confirmed the hyperphagic effect to be anatomically localized to the anteromedial quadrant of the dorsal neostriatum, whereas other quadrants were relatively ineffective. These findings reveal that opioid signals in anteromedial dorsal neostriatum are able to code and cause motivation to consume sensory reward.