Brain site-specific regulation of hedonic intake by orexin and DYN peptides: role of the PVN and obesity

ABSTRACT

The orexin peptides promote hedonic intake and other reward behaviors through different brain sites. The opioid dynorphin peptides are co-released with orexin peptides but block their effects on reward in the ventral tegmental area (VTA). We previously showed that in the paraventricular hypothalamic nucleus (PVN), dynorphin and not orexin peptides enhance hedonic intake, suggesting they have brain-site-specific effects. Obesity alters the expression of orexin and dynorphin receptors, but whether their expression across different brain sites is important to hedonic intake is unclear. We hypothesized that hedonic intake is regulated by orexin and dynorphin peptides in PVN and that hedonic intake in obesity correlates with expression of their receptors. Here we show that in mice, injection of DYN-A_1–13 (an opioid dynorphin peptide) in the PVN enhanced hedonic intake, whereas in the VTA, injection of OXA (orexin-A, an orexin peptide) enhanced hedonic intake. In PVN, OXA blunted the increase in hedonic intake caused by DYN-A_1–13. In PVN, injection of norBNI (opioid receptor antagonist) reduced hedonic intake but a subsequent OXA injection failed to increase hedonic intake, suggesting that OXA activity in PVN is not influenced by endogenous opioid activity. In the PVN, DYN-A_1–13 increased the intake of the less-preferred food in a two-food choice task. In obese mice fed a cafeteria diet, orexin 1 receptor mRNA across brain sites involved in hedonic intake correlated with fat preference but not caloric intake. Together, these data support that orexin and dynorphin peptides regulate hedonic intake in an opposing manner with brain-site-specific effects.

KEYWORDS:

• Orexin
• hypocretin
• dynorphin
• cafeteria diet
• hypothalamus
• obesity
• hedonic intake
• food choice
• feeding behavior
• fat
• orexin 1 receptor
• opioid receptors

Abbreviations::

• CeA, central amygdala
• DH, dorsal hypothalamus
• DYN, dynorphin
• KOR, kappa opioid receptor
• LH, lateral hypothalamus
• OR, opioid receptor
• norBNI, nor-binaltorphimine
• NAc, nucleus accumbens
• OFC, orbitofrontal cortex
• OX1R, orexin 1 receptor
• OX2R, orexin 2 receptor
• OXA, 1orexin-A
• PVN, paraventricular hypothalamic nucleus
• PVT, paraventricular thalamic nucleus
• VH, ventral hypothalamus
• VTA, ventral tegmental area

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the CONICYT FONDECYT Regular Grants 1152075 and 1200578 to C.P.L. and CONICYT FONDECYT Regular 1160820 to E.M.), National Institutes of Health (NS099468-01A1 to J.T.) and the United States Department of Agriculture (ARZT-1372540-R23-131 to J.T.), and by the CONICYT-FONDECYT Postdoctoral Fellowship 3190416 to P.M.

Notes on contributors

P. Mattar

P. Mattar: BS, Universidad de Valparaiso (Nutrition); MS, Universidad de Chile (Nutrition); PhD, Universidad de Chile (Nutrition).

S. Uribe-Cerda

S. Uribe-Cerda: BS, Universidad Andres Bello (Clinical Nutrition).

C. Pezoa

C. Pezoa: BS, Universidad Andres Bello (Engineering in Biotechnology).

T. Guarnieri

T. Guarnieri: BS, Pontificia Universidad Católica de Chile (Biochemistry).

C. M. Kotz

C. M. Kotz: BS, University of Minnesota (Biology); MS, University of Minnesota (Nutrition Science); PhD, University of Minnesota (Nutrition Science).

J. A. Teske

J. A. Teske: BS, University of Minnesota (Biology); MS, University of Minnesota (Exercise Physiology); PhD, University of Minnesota (Nutritional Biochemistry).

E. Morselli

E. Morselli: BS, Universitá di Modena e Reggio Emilia; PhD Université Paris XI (Molecular and Celular Biology).

C. Perez-Leighton

C. Perez-Leighton: BS, Pontificia Universidad Católica de Chile (Biochemistry); PhD, University of Minnesota (Neuroscience).