Operant behavior to obtain palatable food modifies ERK activity in the brain reward circuit

Abstract Food palatability produces behavioral modifications that resemble those induced by drugs of abuse. Palatability-induced behavioral changes require both, the activation of the endogenous cannabinoid system, and changes in structural plasticity in neurons of the brain reward pathway. The ERK intracellular pathway is activated by CB 1 receptors (CB 1 -R) and plays a crucial role in neuroplasticity. We investigated the activation of the ERK signaling cascade in the mesocorticolimbic system induced by operant training to obtain highly palatable isocaloric food and the involvement of the CB 1 -R in these responses. Using immunofluorescence techniques, we analyzed changes in ERK intracellular pathway activation in the mesocorticolimbic system of wild-type and CB 1 knockout mice (CB 1 −/−) trained on an operant paradigm to obtain standard, highly caloric or highly palatable isocaloric food. Operant training for highly palatable isocaloric food, but not for standard or highly caloric food, produced a robust activation of the ERK signaling cascade in the same brain areas where this training modified structural plasticity. These changes induced by the operant training were absent in CB 1 −/−. We can conclude that the activation of the ERK pathway is associated to the neuroplasticity induced by operant training for highly palatable isocaloric food and might be involved in CB 1 -R mediated alterations in behavior and structural plasticity.