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

Abstract

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.

Comparison of the Time-Dependent Changes in Immediate Early Gene Labeling and Spine Density Following Abstinence From Contingent or Non-contingent Chocolate Pellet Delivery

“…Chronic contingent and non-contingent administration of drugs, including amphetamine and cocaine, is associated with increased spine density on MSNs in the NAcSh (Robinson and Kolb, 2004 ). Self-administration of food reward has also been shown to increase dendritic spine density within the NAcSh (Guegan et al, 2013 ; Mancino et al, 2017 ). In incubation of craving models, dendritic spine density has been shown to increase in the NAc following 36 days of withdrawal from cocaine and following 30 days of forced abstinence from normal chow (Christian et al, 2017 ; Dingess et al, 2017 ).…”

“…Incubation of craving for sucrose is associated with elevated c-Fos-positive cells following 30 days of forced abstinence compared to 1 day in both the NAcC and NAcSh (Grimm et al, 2016 ). Self-administration of food reward has been shown to increase dendritic spine density within the NAcSh (Guegan et al, 2013 ; Mancino et al, 2017 ). Both high fat food and chow results in an increase in spines following 30 days of withdrawal (Dingess et al, 2017 ).…”

Evaluating Time-Dependent Changes in Food Seeking Following Periods of Forced Abstinence and Associated Changes in the Nucleus Accumbens

“…This increase in spine density can be seen months after amphetamine has been discontinued and has also been shown to persist a month after cocaine administration (Robinson & Kolb, 2004). Self-administration of highly palatable food has also been shown to increase dendritic spine density within the NAcSh (Mancino et al, 2016). These long-term plastic changes are correlated with behaviours associated with drug use, such as craving, which may lead to relapse (Nestler, Hope, & Widnell, 1993;Robinson & Berridge, 1993;Robinson & Kolb, 2004).…”

“…Chronic contingent and non-contingent administration of drugs, including amphetamine and cocaine, is associated with increased spine density on MSNs in the NAcSh (Robinson and Kolb, 2004). Self-administration of food reward has also been shown to increase dendritic spine density within the NAcSh (Guegan et al, 2013;Mancino et al, 2016). In incubation of craving models, dendritic spine density has been shown to increase in the NAc following 36 days of withdrawal from cocaine and following 30 days of forced abstinence from normal chow (Christian et al, 2016;Dingess et al, 2017b).…”

“…Incubation of craving for sucrose is associated with elevated c-Fos-positive cells following 30 days of forced abstinence compared to 1 day in both the NAcC and NAcSh (Grimm et al, 2016). Self-administration of food reward has been shown to increase dendritic spine density within the NAcSh (Guegan et al, 2013;Mancino et al, 2016). Both high fat food and chow results in an increase in spines following 30 days of withdrawal (Dingess et al, 2017a).…”