Hindbrain orexin 1 receptors influence palatable food intake, operant responding for food, and food-conditioned place preference in rats

Abstract

Rationale: Brain orexin 1 receptors (OX1Rs) are involved in food-motivated behavior. Most research has focused on forebrain OX1R populations, but hindbrain OX1Rs affect feeding. We hypothesized that hindbrain OX1Rs affect the reward value of food.

Objectives: We examined the effects of hindbrain OX1R stimulation or blockade on motivation for food, palatable high-fat (HF) food intake, and food-conditioned place preference.

Methods: Rats trained to lever press for sucrose on a progressive ratio (PR) schedule received fourth intracerebroventricular (icv) injections of vehicle, orexin-A (0.1-1 nmol), or the OX1R antagonist SB334867 (10-20 nmol) before operant test sessions. Effects of these treatments on HF food intake during daily 1-h tests were assessed with fourth icv and nucleus of the solitary tract (NTS) injections. We conditioned a place preference by pairing HF food with one side of a two-sided chamber and then examined the effect of 20 nmol fourth icv SB334867 on the expression of that preference.

Results: In ad lib fed rats on the PR schedule, fourth icv orexin-A significantly increased responding and breakpoint relative to the vehicle. In 24-h food-deprived rats, fourth icv SB334867 significantly decreased responding and breakpoint. Orexin-A delivered to the fourth ventricle (0.1 nmol) or NTS (0.01 nmol) increased HF diet intake. Fourth icv SB334867 did not affect HF food intake, but SB334867 delivered either fourth icv (20 nmol) or intra-NTS (5-10 nmol) suppressed chow intake. Expression of HF food-conditioned place preference was inhibited by fourth icv SB334867.

Conclusions: Hindbrain OX1R activity affects food-motivated operant behavior and may play a role in responding to cues that predict palatable food.

Fig. 1

Effect of fourth icv orexin-A on active lever presses (a), breakpoint (b), and number of reinforcers earned (c) while responding for sucrose on a PR schedule. Data are mean±standard error of the mean (SEM). a, c, Significant differences (p <0.05) among conditions are denoted by different letters above bars. b *p <0.05, compared to vehicle

Fig. 2

Effect of fourth icv SB334867 on active lever presses (a), breakpoint (b), and number of reinforcers earned (c) while responding for sucrose on a PR schedule. Data are mean±SEM. *p <0.05, compared to vehicle

Fig. 3

1-h HF diet intake is increased by fourth icv orexin-A (a) but is not affected by fourth icv SB334867 (b). Fourth icv SB334867 suppresses chow intake during the first 30 min of the dark phase (c). *p <0.05, compared to vehicle

Fig. 4

NTS injection of orexin-A increases 1-h HF food intake (a), and NTS injection of SB334867 suppresses chow intake during the first 30 min of the dark phase (b). *p <0.05, compared to vehicle. c A representative image of a NTS injection site and spread of 0.5 μl True Blue. d A corresponding diagram of the area based on the atlas of Paxinos and Watson (2007). e Also based on the atlas of Paxinos and Watson (2007), a representative image of NTS injection sites for the rats used in these studies is shown, ranging from −13.44 to −14.16 mm relative to bregma. Additional rats' injections were identified in similar locations at points between the anterior and posterior levels shown here. f, g Representative images of thionine-stained sections showing representative NTS injection sites, identified by black arrows, in rats that were injected with 100 % DMSO

Fig. 5

Effect of fourth icv SB334867 on CPP induced by HF food. Time spent in the HF-paired side of the chamber during the pretest vs. the post-training test (a). *p <0.05, compared to pretest time. Percent change in preference from the pretest to posttest (b). *p <0.05, compared to vehicle