Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior

NEUROPHARMACOLOGY

卷:117

Article

Kaska, Sophia¹  Brunk, Rebecca^2,3  Kechner, Megan^2,3  Mazei-Robison, Michelle S.^2,3 

[1] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA

[2] Michigan State Univ, Neurosci Program, E Lansing, MI 48824 USA

[3] Michigan State Univ, Dept Physiol, 567 Wilson Rd,BPS 3182, E Lansing, MI 48824 USA

关键词: Ventral tegmental area;    Stress;    Drinking;    Locomotor activity;    Catecholamine;    Consummatory;   

DOI  :  10.1016/j.neuropharm.2017.02.001

来源: Elsevier

【 摘 要 】

While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naive mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free