MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice

Abstract

The post-oral actions of glucose stimulate intake and condition flavor preferences in rodents. Hypothalamic melanin-concentrating hormone (MCH) neurons are implicated in sugar reward, and this study investigated their involvement in glucose preference conditioning in mice. In Exp. 1 MCH receptor 1 knockout (KO) and C57BL/6 wildtype (WT) mice learned to prefer 8% glucose over an initially more-preferred non-nutritive 0.1% sucralose + saccharin (S+S) solution. In contrast, the KO and WT mice preferred S+S to 8% fructose, which is consistent with this sugar’s weak post-oral reinforcing action. In Exp. 2 KO and WT mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) infusion of 16% glucose and a different flavored solution (CS−) paired with IG water. Both groups drank more CS+ than CS− in training and preferred the CS+ to CS− in a 2-bottle test. These results indicate that MCH receptor signaling is not required for flavor preferences conditioned by the post-oral actions of glucose. This contrasts with other findings implicating MCH signaling in other types of sugar reward processing.

Flavor preferences conditioned by nutritive and non-nutritive sweeteners in mice

“…The preference for the CS+ flavored SS solution over the CS+ fructose solution displayed by the naïve B6 mice in the initial choice was similar to that previously observed in B6 mice for unflavored SS over 8% fructose [40,49]. Thus, the addition of the CS flavors to the two sweeteners did not attenuate the preference for SS over fructose.…”

“…The 0.1% SS mixture was used instead of 0.8% sucralose because it does not have the post-oral inhibitory actions of the concentrated sucralose solution [49] which, as noted above, might impair flavor conditioning. Furthermore, the 0.1% SS mixture is significantly preferred to 8% fructose in brief-access as well as 24-h choice tests suggesting that it has a sweeter taste [40,49]. Based on these findings, we predicted that the SS mixture would condition a stronger CS+ preference than the 8% fructose solution.…”

“…Sucrose, however, was expected to induce a stronger preference because it has both taste and post-oral conditioning effects. We used concentrations of sucrose (8%, 272 mM) and sucralose (0.8%, 20 mM) that are isopreferred by B6 mice in 1-min and 24-h choice tests but have differential IG conditioning actions [40,44,49]. …”

“…B6 mice strongly and persistently prefer unflavored SS to unflavored 8% fructose in 24-h choice tests [40,49]. This observation led to the prediction that SS would condition a stronger CS+ flavor preference than 8% fructose.…”

“…This is not the case, however, for mice given separate 2-day exposure to unflavored SS and fructose. These mice showed only a slight change in their strong SS preference before and after separate exposure to the two sweeteners [40,49]. Thus the reduction in preference for the CS+SS/SS solution (from 89% to 59%) following the one-bottle training indicates that the conditioned preference for the CS+F flavor attenuated the inherent preference of B6 mice for SS over fructose.…”