Decreased consumption of sweet fluids in mu opioid receptor knockout mice: a microstructural analysis of licking behavior

Abstract

Summary Rationale Evidence suggests that the palatability of food (i.e., the hedonic impact produced by its sensory features) can promote feeding and may underlie compulsive eating, leading to obesity. Pharmacological studies implicate opioid transmission in the hedonic control of feeding, though these studies often rely on agents lacking specificity for particular opioid receptors. Objectives Here, we investigated the role of mu opioid receptors (MORs) specifically in determining hedonic responses to palatable sweet stimuli. Methods In Experiment 1, licking microstructure when consuming sucrose solution (2 to 20 %) was compared in MOR knockout and wildtype mice as a function of sucrose concentration and level of food deprivation. In Experiment 2, a similar examination was conducted using the palatable but calorie-free stimulus sucralose (0.001 to 1%), allowing study of licking behavior independent of homeostatic variables. Results In Experiment 1, MOR knockout mice exhibited several alterations in sucrose licking. Although wildtype mice exhibited a two-fold increase in the burst length when food deprived, relative to the nondeprived test, this aspect of sucrose licking was generally insensitive to manipulations of food deprivation for MOR knockout mice. Furthermore, during concentration testing, their rate of sucrose licking was less than half that of wildtype mice. During sucralose testing (Experiment 2), MOR knockout mice licked at approximately half the wildtype rate, providing more direct evidence that MOR knockout mice were impaired in processing stimulus palatability. Conclusions These results suggest that transmission through MORs mediates hedonic responses to palatable stimuli, and therefore likely contributes to normal and pathological eating.

Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity

“…Both enkephalins and β-endorphin are predicted to bind and activate MORs in vivo, and the current findings are in line with recent observations in MOR KO mice (Ostlund et al, 2013). That is, these mice appear to exhibit the combined characteristics of PENK and BEND KOs in that they show fewer bouts of sucrose licking across varying levels of sucrose concentration and food deprivation, which is similar to PENK KO mice, but also show significantly shorter bout lengths than wild types when sucrose concentration or food deprivation state is high, which is similar to BEND KOs.…”

“…In summary, the results of this study are in line with other studies suggesting that endogenous opioids play a role in regulating consummatory behavior and weight gain during access to palatable diets (Atkinson et al, 1985;Czyzyk et al, 2012;Levine et al, 1995;Ostlund et al, 2013;Reid, 1985). Such results are interesting when viewed in the context of human genetic screens strongly implicating opioid receptors in obesity phenotypes (Haghighi et al, 2013;Wheeler et al, 2013).…”

“…Sucralose is a noncaloric sweetener, and can be used to study consummatory behavior supported by hedonic processes in the absence of homeostatic metabolic influences (Bachmanov et al, 2001;Frank et al, 2008;Ostlund et al, 2013). Across one 5-day block of testing, mice were tested twice with a low (0.0003%) and twice with a high (0.003%) concentration of sucralose, counterbalanced for order, all under 4 h food deprivation.…”

“…On all training and testing days, mice were placed in the lickometer for 30 min with continuous and free access to sucrose solution. Mice were trained for two 5-day blocks with 10% sucrose, each daily exposure following 4 h of food deprivation, as previously described (Ostlund et al, 2013). On the first day of all 5-day testing blocks, mice were given a single test session using default training conditions (10% sucrose, 4 h food deprivation) to reestablish baseline responding.…”

“…Opioid transmission has long been implicated in controlling feeding, energy storage, and body weight. However, most evidence implicating endogenous opioids is based on studies using general opiate antagonists such as naloxone and naltrexone (Gosnell and Levine, 2009;Yeomans and Gray, 2002), or genetic knockout of opioid receptors (Czyzyk et al, 2012;Farhang et al, 2010;Ostlund et al, 2013). In short, pharmacological studies are ill equipped to make definitive statements regarding the role of specific endogenous opioid peptides, such as β-endorphin vs enkephalins, in feeding.…”