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

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