Differential involvement of endogenous opioids in sucrose consumption and food reinforcement

Abstract

Endogenous opioids within the central nervous system are postulated to mediate hedonic aspects of feeding behavior. To identify the relevant endogenous opioid receptor ligands, mice lacking one or two of the opioid peptide families β-endorphin, enkephalins or dynorphins were tested for sucrose preference in a two-bottle free-choice drinking paradigm under drug-naïve conditions and following treatment with an opioid antagonist (1 mg/kg naloxone i.p.) or saline. Basal sucrose consumption was unaltered in all of the knockout genotypes compared to their congenic wild-type C57BL/6 littermates during 0.5 and 6 h access to a bottle containing 2, 4, 8, or 16% sucrose and a second bottle containing water. Moreover, all mutant genotypes and wildtype mice exhibited a similar compensatory decrease in overnight food intake following the extra caloric load from 6 h sucrose access. Although these basal responses to sucrose were unaffected by the knockout genotypes, naloxone reduced sucrose consumption by 50% compared to saline treatment during the first 0.5 h in wild-type and β-endorphin knockout mice, but had no effect in enkephalin knockouts, β-endorphin and enkephalin double knockouts, or dynorphin knockouts. These data suggest that naloxone reduces sucrose consumption in wild-type mice by blocking endogenous enkephalin and/or dynorphin signaling, but not β-endorphin. Dynorphin knockouts in the current study had bar-pressing responses for a palatable food reinforcer in an operant procedure under free-feeding conditions similar to wildtype mice while we found in a previous study that β-endorphin and enkephalin knockout mice had reduced motivation to respond (Hayward, et al., 2002). We conclude from these studies directly comparing three strains of opioid peptide knockout mice that enkephalin and dynorphin can modulate sucrose preference but are not necessary to support sucrose consumption. However, dynorphin was not necessary to support wildtype levels of operant responding suggesting that only enkephalin and β-endorphin modulate conditioned food reinforcement. KeywordsOperant behavior; β-endorphin; enkephalin; dynorphin; knockout mice; ingestive behavior * Corresponding author phone: 609-235-1430 fax: 609-235-1498 e-mail: Michael.Hayward@Xenogen.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe plentiful access to calorically dense and highly palatable food choices is a likely contributor to the current obesity epidemic. How ingestion of palatable food is regulated is of great i...

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

“…Previous studies demonstrate that opioids acting at MORs appear to imbue food with a hedonic quality that promotes feeding (Doyle et al, 1993;Giraudo et al, 1999). In addition, recent studies suggest that endogenous opioids, such as enkephalin, can impact the motivational properties of food (Hayward et al, 2006;Mahler and Berridge, 2009;Wassum et al, 2011). Overall, our study provides support for these findings using a novel licking microstructure approach, and elucidates a complex involvement of endogenous opioids in feeding and body weight control.…”

“…Recent studies suggest that endogenous opioids may not only mediate the hedonic properties of food, but also its motivational properties (Hayward et al, 2006;Mahler and Berridge, 2009;Wassum et al, 2011). Again, the largely pharmacological methods employed to date are unable to shed light on the identity of the endogenous opioids involved.…”

The opioid system contributes to the acquisition of reinforcement for dietary fat but is not required for its maintenance

“…The procedure was based on previous reports [28,29] and our previous study [9], with small modifications. To facilitate conducting the training sessions, mice were food-restricted for 5 days to maintain their body weight at 80-90% of their original weight.…”

“…It is possible that the opioid system is involved not only in the palatability of fat but also in developing these behavioral processes. Indeed, β-endorphin-deficient mice showed lower operant responses for fat as a reinforcer when compared to wild-type mice [28,29]. However, it is not clear whether the opioid system contributes to the learning and development of palatability and reinforcement or simply contributes to stimulation itself, because the experimental design in the previous study always inhibited the opioid system during the experimental period.…”

Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration

“…The procedure used in the current study was based on earlier reports (19,20) and our previous study (10), with small modifications. Briefly, mice were food-restricted for 5 d to maintain their body weight at 80-90% of their original weight.…”