Sucrose self-administration and CNS activation in the rat

Abstract

We have previously reported that administration of insulin into the arcuate nucleus of the hypothalamus decreases motivation for sucrose, assessed by a self-administration task, in rats. Because the pattern of central nervous system (CNS) activation in association with sucrose self-administration has not been evaluated, in the present study, we measured expression of c-Fos as an index of neuronal activation. We trained rats to bar-press for sucrose, according to a fixed-ratio (FR) or progressive-ratio (PR) schedule and mapped expression of c-Fos immunoreactivity in the CNS, compared with c-Fos expression in handled controls. We observed a unique expression of c-Fos in the medial hypothalamus (the arcuate, paraventricular, retrochiasmatic, dorsomedial, and ventromedial nuclei) in association with the onset of PR performance, and expression of c-Fos in the lateral hypothalamus and the bed nucleus of stria terminalis in association with the onset of FR performance. c-Fos expression was increased in the nucleus accumbens of both FR and PR rats. Our study emphasizes the importance of both hypothalamic energy homeostasis circuitry and limbic circuitry in the performance of a food reward task. Given the role of the medial hypothalamus in regulation of energy balance, our study suggests that this circuitry may contribute to reward regulation within the larger context of energy homeostasis.

Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist

“…Interestingly, antagonism of the melanin-concentrating hormone (MCH) one receptor decreases operant responding for sucrose solution, but not saccharin solution, indicating that the MCH system in contrast to the orexin system may play a stronger role in homeostatic than non-homeostatic feeding (Karlsson et al 2012). Central administration of the anorexigenic peptides insulin and leptin also decrease operant responding for palatable foods including sucrose (Figlewicz et al, 2006; Figlewicz and Benoit, 2009; Figlewicz et al, 2011). Interestingly, intraventricular injections of insulin attenuate sucrose self-administration but at doses (insulin 5 mU, or leptin 0.2 μg) that are sub-threshold for regulating homeostatic feeding behaviors [Figlewicz et al, 2006].…”

Effect of recurrent yohimbine on immediate and post-hoc behaviors, stress hormones, and energy homeostatic parameters

“…Procedures were based upon our published methodology [23,24]. All self-administration sessions were carried out between 0700 and 1200 hr.…”

“…Fluorescence ICC was used to identify and quantitate Fos-positive neuronal cell bodies in response to a history of YOH vs. SAL injections, according to our established methodology [23,24], as a marker of brain regional activation. On the Monday following the injection series (i.e., three days after the last injection), rats were moved into the experiment room at the same time as for previous injections, and put in the same cages in which they had received injections.…”

Modulation of Food Reward by Endocrine and Environmental Factors

“…Numerous detailed and contemporary reviews and discussion of this circuitry are available (see [23]); the interested reader is directed to the cited references, with apology to many colleagues for the inability to cite all pertinent studies. However, a point to be emphasized is that medial hypothalamic structures also contribute substantially to the mediation of food reward, including the arcuate nucleus (ARC) and ventromedial nucleus (VMN) (24,25). Research from my lab and others has shown that the neurotransmitter agouti-related peptide (AGRP) is important for motivational behaviors assessed in the mouse and rat (26–29).…”