Investigating the role of the central melanocortin system in stress and stress-related disorders

Emanuela Micioni Di Bonaventura; Luca Botticelli; Fabio Del Bello; Gianfabio Giorgioni; Alessandro Piergentili; Wilma Quaglia; Adele Romano; Silvana Gaetani; Maria Vittoria Micioni Di Bonaventura; Carlo Cifani

doi:10.1016/j.phrs.2022.106521

Investigating the role of the central melanocortin system in stress and stress-related disorders

Pharmacol Res. 2022 Nov:185:106521. doi: 10.1016/j.phrs.2022.106521. Epub 2022 Oct 20.

Affiliations

¹ School of Pharmacy, Pharmacology Unit, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino, Italy. Electronic address: emanuela.micioni@unicam.it.
² School of Pharmacy, Pharmacology Unit, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino, Italy. Electronic address: luca.botticelli@unicam.it.
³ School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: fabio.delbello@unicam.it.
⁴ School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: gianfabio.giorgioni@unicam.it.
⁵ School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: alessandro.piergentili@unicam.it.
⁶ School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: wilma.quaglia@unicam.it.
⁷ Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy. Electronic address: adele.romano@uniroma1.it.
⁸ Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy. Electronic address: silvana.gaetani@uniroma1.it.
⁹ School of Pharmacy, Pharmacology Unit, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino, Italy. Electronic address: mariavittoria.micioni@unicam.it.
¹⁰ School of Pharmacy, Pharmacology Unit, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino, Italy. Electronic address: carlo.cifani@unicam.it.

PMID: 36272641
DOI: 10.1016/j.phrs.2022.106521

Abstract

The melanocortinergic neural circuit, known for its influence on energy expenditure and feeding behavior, also plays a role in stress and stress-induced psychiatric disorders, including anxiety and depression. The major contribution is given by the melanocortin-4 receptor (MC4R) subtype, highly expressed in brain regions involved in the control of stress responses. Furthermore, the MC4R appears to profoundly affect the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and it has been also highlighted a functional and anatomical interaction with the corticotropin-releasing factor (CRF), an important mediator of stress and stress-related behaviors. The MC4R agonists seem to exacerbate stress-inducing anxiety- and depressive-like behavior, while MC4R antagonists have been demonstrated to mitigate such disorders, as shown in several preclinical behavioral tests. The evidence collected in the present review suggests that the melanocortin system, through the MC4R, could possibly modulate behavioral responses to stress, suggesting the use of MC4R antagonists as a possible novel treatment for anxiety and depression induced by stress.

Keywords: ASTRESSIN (PubChem CID: 16133798); Anxiety; CRF; Depression; HS014 (PubChem CID: 24868239); HS024 (PubChem CID: 25081552); MC4R; MCL0020 (PubChem CID: 10145571); MCL0042 (PubChem CID: 9917301); MCL0129 (PubChem CID: 6918688); MTII (PubChem CID: 92432); Melanocortin system; NDP-MSH (PubChem CID: 44277697); RO27–3225 (PubChem CID: 9962372); RU486 (PubChem CID: 55245); SHU9119 (PubChem CID: 6440621); Stress.

Publication types

Review

MeSH terms

Anxiety / drug therapy
Humans
Hypothalamo-Hypophyseal System
Melanocortins*
Pituitary-Adrenal System*
Stress, Physiological

Substances

Melanocortins