Alpha2-adrenergic dysregulation in congenic DxH recombinant inbred mice selectively bred for a high fear-sensitized (H-FSS) startle response

Publication date: Available online 2 December 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Rochelle N. Wickramasekara, Charles Bockman, Joachim Hanke, Herbert Schwegler, JoAnn McGee, Edward Walsh, Deniz Yilmazer-HankeAbstractPatients with anxiety disorders and posttraumatic stress disorder (PTSD) exhibit exaggerated fear responses and noradrenergic dysregulation. Fear-related responses to α2-adrenergic challenge were therefore studied in DxH C3H/HeJ-like recombinant inbred (C3HLRI) mice, which are a DBA/2J-congenic strain selectively bred for a high fear-sensitized startle (H-FSS). C3HLRI mice showed an enhanced acoustic startle response and immobility in the forced swim test compared to DBA/2J controls. The α2-adrenoceptor antagonist yohimbine (Yoh; 5.0 mg/kg) induced an anxiogenic and the α2-adrenoceptor agonist clonidine (Clon; 0.1 mg/kg) an anxiolytic effect in the open field (OF) in C3HLRI but not DBA/2J mice. In auditory fear-conditioning, Yoh (5.0 mg/kg)-treated C3HLRI mice showed higher freezing during fear recall and extinction learning than DBA/2J mice, and a higher ceiling for the Yoh-induced deficit in fear extinction. No strain differences were observed in exploration-related anxiety/spatial learning or the Clon-induced (0.1 mg/kg) corticosterone surge. A global analysis of the behavioral profile of the two mouse strains based on observed and expected numbers of significant behavioral outcomes indicated that C3HLRI mice showed significa...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research