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

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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.

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Acknowledgments

This work was funded by NIH grants DK078779 and DK095757 to D.L.W.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Psychology and Program in Neuroscience, Florida State University, Box 3064301, Tallahassee, FL, 32306-4301, USA

    Kristen Kay, Eric M. Parise, Nicole Lilly & Diana L. Williams

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  1. Kristen Kay
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  2. Eric M. Parise
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  3. Nicole Lilly
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  4. Diana L. Williams
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Corresponding author

Correspondence to Diana L. Williams.

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Figure 1

Representative thionin-stained coronal sections through NTS of a rat that was injected with 100 % DMSO into the 4th ventricle 20 min before transcardial perfusion with PBS followed by 4 % paraformaldehyde (JPEG 914 kb)

High resolution image (TIFF 5359 kb)

Figure 2

Representative images of coronal sections through NTS of rats that received 4th-ventricle injection of either saline (A) or 66 % DMSO and 3.4 % hydroxypropyl-β cyclodextrin in sterile deionized water (B) prior to IP injection of 5 μg/kg amylin 90 min before transcardial perfusion with PBS followed by 4 % paraformaldehyde. These sections were immunostained for dopamine beta-hydroxylase (DbH, green) and c-Fos (red). Rats treated with 4th-icv DMSO had previously been in a behavioral study in which they received at least two 4th-icv DMSO and SB334867 (dissolved in the DMSO vehicle) injections. DMSO treatment had no impact on DbH expression or c-Fos induction by amylin. DMV = dorsal motor nucleus of the vagus nerve. (JPEG 17 kb)

High resolution image (TIFF 5940 kb)

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Kay, K., Parise, E.M., Lilly, N. et al. Hindbrain orexin 1 receptors influence palatable food intake, operant responding for food, and food-conditioned place preference in rats. Psychopharmacology 231, 419–427 (2014). https://doi.org/10.1007/s00213-013-3248-9

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  • DOI: https://doi.org/10.1007/s00213-013-3248-9

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