Abstract
Orexin neurons originate in the lateral and dorsomedial hypothalamus and perifornical area and produce two different neuropeptides: orexin A (OxA) and orexin B (OxB), which activate OxR1 and OxR2 receptors. In the lateral hypothalamus (LH) orexin neurons are involved in behavior motivated by natural rewards such as palatable food (sugar, high-fat food) and it has been demonstrated similarly that the orexin signaling in the ventral tegmental area (VTA) is implicated in the intake of high-fat food. The VTA is an important area involved in reward processing. Given the involvement of nucleus accumbens (NAc) shell dopamine (DA) in motivation for food, we intended to investigate the effect of OxA on the basal and feeding-activated DA transmission in the NAc shell. OxA is a large peptide and does not cross the blood–brain barrier and for this reason was loaded on two kinds of liposomes: anti-transferrin-monoclonal antibodies (OX26-mAb) and lactoferrin-modified stealth liposomes. The effect of IV administration of both OxA liposomes on NAc shell DA was studied by microdialysis in freely moving rats. OxA, administered using both kinds of liposomes, produced a delayed and transitory increase in dialysate DA in the NAc shell, strongly and lastingly potentiated the increase in dialysate DA elicited by sucrose pellet consumption and increased the number of eaten pellets. These effects of OxA on DA transmission and feeding were prevented by the OxR1 antagonist SB 334867. Hence, OxA acting on VTA OxR1 can facilitate sucrose-stimulated NAc shell DA transmission directly by increasing the basal activity of VTA DA neurons that send their projections to the NAc shell.
Highlights
Many neuronal systems are involved in the regulation of behavioral responses essential for the survival of the individual and of the species
We recently reported that the extracellular DA increases selectively in the nucleus accumbens (NAc) shell of rats responding for sucrose pellets by nose poking [33,34,35]
Post-hoc testing revealed a stimulation of DA transmission only when the orexin A (OxA) was delivered by liposomes
Summary
Many neuronal systems are involved in the regulation of behavioral responses essential for the survival of the individual and of the species. Orexin neurons are located in the perifornical nucleus, the dorsomedial hypothalamic nucleus, and the dorsal and lateral hypothalamic areas and project widely through the central nervous system (CNS), including the cerebral cortex, the hippocampus, the thalamus, the midbrain, and the spinal cord [9,10,11,12]. Orexin neurons produce two peptides from a common preproorexin molecule; these peptides are orexin A (OxA) and orexin B (OxB), which are 33 and 28 amino acids in length, respectively. Harris and Aston–Jones [4] highlighted a dichotomy in the functions of orexin neurons. These authors reported that orexin neurons in the lateral hypothalamus are implicated in food responsiveness, while orexin neurons in the perifornical and dorsomedial hypothalamus play an important role in arousal and stress responsiveness
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