BNST CRF receptor type 1 modulates mechanical hypersensitivity induced by adolescent alcohol exposure in adult female mice

Author(s)

Bertagna, Natalia B. ; Holmgren, Eleanor B. ; Engi, Sheila A. ; Ha, Linh ; Cruz, Fabio C. ; Albrechet-Souza, Lucas ; Wills, Tiffany A.

• Document type: Journal article
• Source: Psychopharmacology; v. 241, n. 12, p. 11-pg., 2024-09-30.

Abstract

RationaleAlcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST).ObjectivesThis study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity.ResultsFemale mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-na & iuml;ve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity.ConclusionsThese findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain. (AU)

• FAPESP's process: 21/13317-9 - Acute restraint stress during adulthood modulates glutamate release through CRF type 1 receptors in bed nucleus of stria terminalis of male and female mice with history of adolescent alcohol exposure
• Grantee: Natalia Bonetti Bertagna
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories
• Grantee: Fabio Cardoso Cruz
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2