Elsevier

Neuroscience

Volume 210, 17 May 2012, Pages 243-248
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Orexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat

https://doi.org/10.1016/j.neuroscience.2012.02.036Get rights and content

Abstract

Data from our laboratory indicate that the orexin system is involved in the regulation of both conditioned and unconditioned responding for palatable foods. Anticipation of food rewards activates orexin receptor containing neurons within the paraventricular nucleus of the thalamus (PVT). The PVT regulates mesolimbic dopamine neurochemistry through direct connections with the nucleus accumbens and modulates the processing of cognitive-emotional information, suggesting that the PVT may represent a unique brain region with the capacity to mediate orexinergic effects on brain dopamine and behavior. Here, we tested the hypothesis that PVT orexin signaling mediates mesolimbic dopamine and reward-based feeding. To do this we used a behavioral pharmacological approach in tandem with central genetic manipulation of the orexin-1 receptor in the PVT. Data from these studies indicate that orexin-A action in the PVT increases dopamine levels in the nucleus accumbens. In addition, endogenous orexin signaling in the PVT mediates locomotor activity and hedonic feeding responses. Together these data highlight the PVT as a critical site capable of mediating orexin action on brain dopamine and reward-based feeding.

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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