Role of DOR in neuronal plasticity changes promoted by food-seeking behaviour.

Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genotypes were revealed on operant behaviour acquisition in FR1. DOR knockout mice displayed lower number of active lever-presses than wild-type mice on FR5, and a similar decrease was revealed in DOR KO mice in the breaking point during the PR. This operant training to obtain palatable food increased dendritic spine density in the PFC, HCP and NAc shell of wild-type, but these plasticity changes were abolished in DOR KO mice. Our results support the hypothesis that DOR regulates the reinforcing effects and motivation for palatable food through neuroplastic changes in specific brain reward areas.