Opioid system in the medial prefrontal cortex mediates binge-like eating

Abstract

Binge eating disorder is an addiction-like disorder characterized by excessive food consumption within discrete periods of time. This study was aimed at understanding the role of the opioid system within the medial prefrontal cortex (mPFC) in the consummatory and motivational aspects of binge-like eating. For this purpose, we trained male rats to obtain either a sugary, highly palatable diet (Palatable rats) or a chow diet (Chow rats) for 1 hour/day. We then evaluated the effects of the opioid receptor antagonist, naltrexone, given either systemically or site-specifically into the nucleus accumbens (NAcc) or the mPFC on a fixed ratio 1 (FR1) and a progressive ratio schedule of reinforcement for food. Finally, we assessed the expression of the genes proopiomelanocortin (POMC), pro-dynorphin (PDyn) and pro-enkephalin (PEnk), coding for the opioids peptides in the NAcc and the mPFC in both groups. Palatable rats rapidly escalated their intake by four times. Naltrexone, when administered systemically and into the NAcc, reduced FR1 responding for food and motivation to eat under a progressive ratio in both Chow and Palatable rats; conversely, when administered into the mPFC, the effects were highly selective for binge eating rats. Furthermore, we found a twofold increase in POMC and a ∼50% reduction in PDyn gene expression in the mPFC of Palatable rats, when compared to control rats; however, no changes were observed in the NAcc. Our data suggest that neuroadaptations of the opioid system in the mPFC occur following intermittent access to highly palatable food, which may be responsible for the development of binge-like eating.

Keywords: Addiction; binge eating disorder; nucleus accumbens; opioid; palatability; prefrontal cortex.

Figure 1

Effects of systemic treatment with naltrexone (0, 0.03, 0.1, 0.3 mg/kg, subcutaneously) on (A) food self-administration (n=20) and (B) breakpoint on a progressive ratio schedule of reinforcement (n=19) in male Wistar rats. Panels represent M±SEM. Symbols denote: ^* significant difference from vehicle condition p<0.05, ^** p<0.01, ^*** p<0.001 (Student Newman–Keuls test).

Figure 2

Effect of microinfusion with naltrexone (0, 5, 25 µg/side) in NAcc shell on (A) food self-administration (n=18) and (B) breakpoint on a progressive ratio schedule of reinforcement (n=17) in male Wistar rats. Panel represents M±SEM. Symbols denote: ^* significant difference from vehicle condition p<0.05, ^** p<0.01 (Student Newman–Keuls test).

Figure 3

Effect of microinfusion with naltrexone (0, 5, 25 µg/side) in mPFC on (A) food self-administration (n=17) and (B) breakpoint on a progressive ratio schedule of reinforcement (n=17) in male Wistar rats. Panel represents M±SEM. Symbols denote: ^* significant difference from vehicle condition p<0.05, ^** p<0.01 (Student Newman–Keuls test).

Figure 4

Drawing of coronal rats’ brain slices. Dots represent the injection sites in (A) NAcc shell and (B) mPFC included in the data analysis.

Figure 5

POMC, PDyn, and PEnk mRNA expression in the NAcc (A, B and C) and in the mPFC (D, E and F) of male Wistar rats. Brain areas were collected 24 h after the last daily binge-like eating session. Data represent M±SEM expressed as percent of Chow group; * p<0.05 vs Chow group (Student’s t-test).