Role of opioid receptors in sweet food intake in rats exposed to chronic restraint stress

Abstract

The present study aimed to investigate the roles of the endogenous opioid system and its receptors (OR) in the development of sweet food intake in rats exposed to chronic restraint stress. The sweet food intake behavioral paradigm and the measurement of dopaminergic neurotransmitter levels in mesocorticolimbic system of rat treated with or without opioid receptor blockers were assessed. Male adult Wistar rats were divided into two groups: control (CON) and stress (ST) which rat were restrain 1 h/day, for 14 days. Both groups were subdivided into two groups; treated with or without non-selective or selective µ-, δ- or k-OR blockers (naloxone; NX, CTOP, naltridole; NT or nor-binaltorphimine dihydrochloride; nor-BNI, 0.5-1 mg/ml, s.c., 30 min before the bahavioral test). In the sweet food intake test, the rats were placed in the cage and allowed to consume sweet food (Froot loops® pellets), the number of ingested pellets during a period of 6 min was then recorded. Sweet food consumption was increased in chronic restraint stress-rats compared to control rats. Even though, there were no differences in the consumption of standard rat chow between groups. Adrenal gland mass associated with serum corticosterone level significantly increased in restraint stress-rats. These changes of adrenal gland mass and serum corticosterone confirmed the effective of stress model. Interestingly, the increase of sweet food consumption induced by restraint stress was inhibited by non-selective OR blocker (NX, 0.5 mg/ml) but not by any of selective OR blockers. To assess dopaminergic system, brain dopamine (DA) and its metabolites (DOPAC or HVA) level in amygdala, frontal cortex, hippocampus, and nucleus accumbens were measured by HPLC-EC. The dopamine levels were significntly increased in nucleus accumbens of chronic stressed-rat. Moreover, the sweet food consumption tended to increase the DA levels in nucleus accumbens in both stress and non-stress rats. On the other hand, dopaminergic activity (DOPAC/DA and HVA/DA ratios) of chronic stress-rats was lower than control rats. Additionally, the HVA levels in the hippocampus and the dopaminergic activity, shown by DOPAC/DA and HVA/DA ratios in the amygdala were significantly decreased in chronic stressed-rats. Further, nor-BNI tended to decrease dopamine levels in control rats, while other opioid antagonist did not affect. In contrast, naltridole could suppress DA level in nucleus accumbens in chronic stress rats while nor-BNI has no effect. These results suggested that chronic stress causes an increase in sweet food intake, and opioid system partially regulated stress induced-sweet food intake. Moreover, chronic stress may cause adaptation of δ- and k-OR in opioid systems as they differentially affected dopaminergic activity in mesolimbic system following OR antagonists administration. Nevertheless, this study has established the relationship between stress and opioid system in modulating mesolimbic dopamine system that affected sweet food intake.