Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

• Published in: Frontiers in neuroscience Vol. 14; p. 581977
• Main Authors: Guo, Jing, Ba, Xiyuan, Matsuda, Megumi, Wei, Pengfei, Jiang, Changyu, Sun, Wuping, Xiao, Lizu, Xiong, Donglin, Liao, Xiang, Hao, Yue
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 23.09.2020; Frontiers Media S.A
• Subjects: Ablation; Behavior; c-Fos protein; Drug development; Drug dosages; gastrin-releasing peptide; Gene expression; Grooming; hindpaw scratching; Hybridization; itch; Laboratory animals; Mental disorders; Morphine; mRNA; Neurons; Neuroscience; Oxytocin; oxytocin receptor; Pain; Reagents; Scratching behavior; Sexual behavior; Social behavior; Spinal cord; spinal dorsal horn; Statistical analysis; Variance analysis; United States > US; China
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2020.581977

Oxytocin (OT), a neuropeptide involved in the regulation of complex social and sexual behavior in mammals, has been proposed as a treatment for a number of psychiatric disorders including pain. It has been well documented that central administration of OT elicits strong scratching and grooming behaviors in rodents. However, these behaviors were only described as symptoms, few studies have investigated their underlying neural mechanisms. Thus, we readdressed this question and undertook an analysis of spinal circuits underlying OT-induced scratching behavior in the present study. We demonstrated that intrathecal OT induced robust but transient hindpaw scratching behaviors by activating spinal OT receptors (OTRs). Combining the pre-clinical and clinical evidence, we speculated that OT-induced scratching may be an itch symptom. Further RNAscope studies revealed that near 80% spinal GRP neurons expressed OTRs. OT activated the expression of c-fos mRNA in spinal GRP neurons. Chemical ablation of GRPR neurons significantly reduced intrathecal OT-induced scratching behaviors. Given GRP/GRPR pathway plays an important role in spinal itch transmission, we proposed that OT binds to the OTRs expressed on the GRP neurons, and activates GRP/GRPR pathway to trigger itch-scratching behaviors in mice. These findings provide novel evidence relevant for advancing understanding of OT-induced behavioral changes, which will be important for the development of OT-based drugs to treat a variety of psychiatric disorders.