Orexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat

Abstract

Data from our lab 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.

Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

“…The present results suggest that Orx/Hcrt inputs to the PVT facilitate cortical activation that is linked to general arousal (Sato-Suzuki et al, 2002), which could explain the reinstatement of cocaine seeking. Moreover, Orx-A/Hcrt-1 administration in the PVT significantly increased dopamine levels in the nucleus accumbens (Choi et al, 2012), suggesting that the PVT is a key relay for Orx/Hcrt's effects on the mesolimbic dopamine system and reward-seeking behavior.…”

Distribution of the orexin-1 receptor (OX1R) in the mouse forebrain and rostral brainstem: A characterisation of OX1R-eGFP mice

“…Indeed, excitotoxic lesions of the PVT attenuate context-induced reinstatement of alcohol-seeking (Hamlin et al, 2009) and inhibition of the PVT with tetrodotoxin or cocaine-and amphetamine-regulated transcript (CART) blunts cocaine-primed reinstatement (James et al, 2010). The PVT is involved in mediating the effects of orexin on reward-based feeding and knockdown of OX 1 R attenuates highfat diet consumption in sated rats (Choi et al, 2012). Drugassociated contextual cues activate PVT neurons which are closely apposed by orexin fibres (Dayas et al, 2008), and intra-PVT microinjections of orexin reinstate reward-seeking behaviour for both a drug (cocaine) and highly palatable food (sweetened condensed milk) reward (Martin-Fardon et al, 2011).…”

Limbic thalamus and state-dependent behavior: The paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks

“…Orexin-A administration into PVT in the rat increases dopamine levels in the nucleus accumbens (Choi et al, 2012) and inhibits locomotor activity (Choi et al, 2012;Li et al, 2009), suggesting that orexin release in the midline thalamus could limit locomor activity to enhance vigilance allowing the expression of other behaviors (Li et al, 2009). Endogenous orexin signaling in PVT mediates hedonic feeding responses in the rat (Choi et al, 2012).…”

“…Endogenous orexin signaling in PVT mediates hedonic feeding responses in the rat (Choi et al, 2012). On the other hand, endogenous orexin release in PVT has been implicated in the regulation of anxiety level in the rat, as part of "an orexin-PVT emotional arousal system" (Li et al, 2010a;Fig.…”