Palatability enhances food intake by hedonic mechanisms that prevail over caloric necessities. Different studies have demonstrated the role of endogenous cannabinoids in the mesocorticolimbic system in controlling food hedonic value and consumption. We hypothesize that the endogenous cannabinoid system could also be involved in the development of food-induced behavioral alterations, such as food-seeking and binge-eating, by a mechanism that requires neuroplastic changes in the brain reward pathway. For this purpose, we evaluated the role of the CB1 cannabinoid receptor (CB1-R) in the behavioral and neuroplastic changes induced by operant training for standard, highly caloric or highly palatable isocaloric food using different genetics, viral and pharmacological approaches. Neuroplasticity was evaluated by measuring changes in dendritic spine density in neurons previously labeled with the dye DiI. Only operant training to obtain highly palatable isocaloric food induced neuroplastic changes in neurons of the nucleus accumbens shell and prefrontal cortex that were associated to changes in food-seeking behavior. These behavioral and neuroplastic modifications induced by highly palatable isocaloric food were dependent on the activity of the CB1-R. Neuroplastic changes induced by highly palatable isocaloric food are similar to those produced by some drugs of abuse and may be crucial in the alteration of food-seeking behavior leading to overweight and obesity.

This work was supported by the Spanish Ministerio de Ciencia e Innovació (#SAF2007-64062 and #SAF2008-00962), the Instituto de Salud CarlosIII (#RD06/001/001), the Plan Nacional sobre Drogas, the Catalan Government (SGR2009-00131 and SGR2009-224), the ICREA Foundation (ICREA Academia-2008), the DG Research of the European Commission (GENADDICT,/n#LSHM-CT-2004-05166; and PHECOMP, #LSHM-CT-2007-037669) the FIS’’ (PI07/0715),ATIP-Avenir and Sanofi-Aventis grants.This work was also supported by the Plan Nacional Sobre Drogas (#2009/026) to R.M.