Electrophysiological effects of melanocortin receptor ligands on neuronal activities of monoaminergic neurons in rats.
The melanocortin-4 (MC4) receptor may possibly be involved in stress and stress-related behavior. In the present study, we examined effects of an intracerebroventricular injection of the MC4 receptor agonist, Ac-[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH 4-10-NH2 (MT II), and the MC4 receptor inverse agonist, Agouti-related protein (AGRP), on dorsal raphe nucleus (DRN) serotonergic neurons and the locus coeruleus (LC) noradrenergic neurons, both of which are brain neuronal systems related to responses to stress. The firing rate of DRN serotonergic neurons was increased by MTII, while AGRP had a lack of effect on the firing rate of DRN serotonergic neurons. In comparison with the DRN, MTII significantly reduced the firing rate of LC noradrenergic neurons, while AGRP increased LC neuronal activity. These findings suggest that MC4 receptor ligands differently regulate serotonergic and noradrenergic neuronal systems. The MC4 receptor mediating multiple regulation on the monoaminergic neuronal system may, in part, relate to stress responses (anxiety and/or depressive behavior).
Kawashima
Naoya
N
Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. n.kawashima@po.rd.taisho.co.jp
Chaki
Shigeyuki
S
Okuyama
Shigeru
S
D054369:Agouti-Related Protein; D000818:Animals; D004594:Electrophysiology; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D000521:alpha-MSH / Q000031:analogs & derivatives
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009842:Oligopeptides; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D012701:Serotonin; D000521:alpha-MSH