Cognitive, Behavioral, and Systems NeuroscienceResearch PaperOrexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat
Highlights
▶In this manuscript, Choi et al., report that orexin signaling within the paraventricular thalamic nucleus increases dopamine content in the nucleus accumbens. ▶The authors further report that orexin signaling in the PVT modulates locomotor activity and hedonic feeding behavior. ▶These are the first data to implicate PVT orexin signaling in the regulation of mesolimbic function and hedonic feeding.
Section snippets
Animals
Male Long-Evans rats (Harlan, Indianapolis, IN, USA) weighing 300–350 g were housed individually in a vivarium on a 12-h light/dark cycle schedule. Room temperature was maintained at 25 °C. All animals were given ad libitum access to pelleted standard rodent chow and water unless noted. Rats were maintained on chow (Teklad, 3.41, 0.51 kcal/g from fat) unless otherwise noted. The hedonic feeding experiments used high-fat diet (HFD) (Research Diets, New Brunswick, NJ, USA; 4.41, 1.71 kcal/g from
Intra-PVT orexin-A increases NAcc dopamine
To test the hypothesis that PVT orexin signaling mediates mesolimbic dopamine, we injected orexin-A directly into the PVT and measured dopamine levels in the NAcc. The 1 nm dose of orexin-A (1 nmol) had no effect on NAcc dopamine. However, the 5 nmol dose of orexin-A administered directly into the PVT significantly increased dopamine levels in the NAcc (F(1,4)=8.21, P<0.05; Fig. 1B). Following orexin injection, NAcc dopamine levels were 48.83 ng/mg protein±30.85 (1 nm) and 66.48 ng/mg
Discussion
Data from the current manuscript indicate that (1) intra-PVT orexin-A increases mesolimbic dopamine, (2) OX1R knockdown increases basal locomotor activity, and (3) attenuates hedonic feeding. Together, these results implicate the PVT as a critical mediator of orexin effects on mesolimbic dopamine and food reward. Moreover, we propose that the current data support a generalized role for orexin—PVT signaling to promote cognitive arousal secondary to inducing mesolimbic dopamine activity.
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Conclusion
When viewed collectively the present results indicate that orexin signaling in the PVT is capable of modulating brain dopamine and behavior. The ability of orexin to act within PVT neurons to modulate NAcc dopamine represents a novel signaling mechanism by which orexin mediates dopamine neurochemistry and validates the significance of the proposed hypothalamic-thalamic-striatal axis concept for the control of food reward (Kelley et al., 2005). Our behavioral results from knockdown studies
Acknowledgments
This research was supported by NIH DK066223 to S.C.B.
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