Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons.

Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI), but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated. The effects of most classical neurotransmitters on MCH neurons have been studied, but those of most neuropeptides are poorly understood. To gain insight into how neuropeptides regulate the MCH system, we investigated which neuropeptide receptors are expressed by MCH neurons by using double in situ hybridization. In all, 20 receptors, selected based on either a suspected interaction with the MCH system or demonstrated high expression levels in the LH and ZI, were tested to determine whether they are expressed by MCH neurons. Overall, 11 neuropeptide receptors were found to exhibit significant colocalization with MCH neurons: nociceptin/orphanin FQ opioid receptor (NOP), MCHR1, both orexin receptors (ORX), somatostatin receptors 1 and 2 (SSTR1, SSTR2), kisspeptin recepotor (KissR1), neurotensin receptor 1 (NTSR1), neuropeptide S receptor (NPSR), cholecystokinin receptor A (CCKAR), and the κ-opioid receptor (KOR). Among these receptors, six have never before been linked to the MCH system. Surprisingly, several receptors thought to regulate MCH neurons displayed minimal colocalization with MCH, suggesting that they may not directly regulate the MCH system.