Orexin Receptor-1 (OX1R)

Orexin or hypocretin; a peptide that resembles the molecular structure of the gastric peptide secretin, was discovered in 1996 by two independent groups of researchers. One group named it orexin after the Greek word orexis which means “appetite,” while the other group named it hypocretin since it was synthesized in the hypothalamus and resembles secretin (Sakurai et al. 1998). Both the nomenclatures for orexins are currently in use. We would adhere to “orexin” for references to the peptides in this article. These hypothalamic peptides are produced by orexin neurons in the dorsomedial (DMH), lateral (LH), and perifornical hypothalamic areas (PFA) (Sakurai et al. 1998). Since these areas of the hypothalamus are involved in arousal, sleep-wake cycle, thermoregulation, feeding and appetite, the function of orexins is implicated in the regulation of these behaviors. Furthermore, studies have shown that orexins are also involved in emotion, reward and drug seeking. Since these neuropeptides control a wide range of functions important for survival, they are implicated in a variety of neuropsychiatric conditions like obesity, drug addiction and sleep disorders (Sakurai et al. 1998). Further research revealed the identification of two types of orexinergic peptides, namely, orexin A and orexin B. The common precursor, prepro-orexin mRNA, is differentially cleaved to yield either orexin A, a 33-amino acid peptide of 3562 Da with two sets of intrachain disulfide bonds (Fig. 1), or orexin B, a 28-amino acid linear peptide of 2937 Da (Ebrahim et al. 2002). Interestingly, the molecular structure of orexin A is conserved among numerous mammalian species. Both the orexinergic subtypes are ligands of the G protein-coupled cell-surface receptor (GPCR), HFGAN72. Later in 1998, this orphan receptor was recognized as orexin receptor-1 (OX1R) or hypocretin receptor-1 because of the pioneering work by Sakurai T. et al. (1998) (Fig. 1). We would adhere to “OX1R” for references to the orexin receptor-1 in this chapter

Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

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