Intra-NAc insulin reduces the motivation for food and food intake without altering cue-triggered food-seeking

Abstract

Insulin receptors are expressed throughout the adult brain, and insulin from the periphery reaches the central nervous system. In humans and rodents, actions of insulin in the brain decrease food intake. Furthermore, insulin receptor activation alters dopamine and glutamate transmission within mesolimbic regions that influence food-seeking and feeding including the nucleus accumbens (NAc). Here we determined how intra-NAc insulin affects conditioned approach (a measure of cue-triggered food-seeking), free food intake, and the motivation to obtain food in hungry rats using Pavlovian and instrumental approaches. Intra-NAc insulin did not affect conditioned approach but did reduce home cage chow intake immediately following conditioned approach testing. Consistent with reduced chow intake, intra-NAc insulin also reduced the motivation to work for flavored food pellets (assessed by a progressive ratio procedure). This effect was partially reversed by insulin receptor blockade and was not driven by insulin-induced sickness or malaise. Taken together, these data show that insulin within the NAc does not alter behavioral responses to a food cue, but instead reduces the motivation to work for and consume food in hungry animals. These data are discussed in light of insulin's role in the regulation of feeding, and its dysregulation by obesity.