Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.
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-naïve 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.
Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, United States.
Sophia
S
Kaska
Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.
Rebecca
R
Brunk
Dept. of Physiology, Michigan State University, East Lansing, MI 48824, United States.
Vedrana
V
Bali
Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.
Megan
M
Kechner
Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States; Dept. of Physiology, Michigan State University, East Lansing, MI 48824, United States. Electronic address: mazeirob@msu.edu.
Michelle S
MS
Mazei-Robison
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects; D004326:Drinking / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008124:Locomotion / Q000502:physiology*; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D012919:Social Behavior; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology; D013395:Sucrose / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D046912:Multiprotein Complexes; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C525637:rictor protein, mouse; D013395:Sucrose; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
Catecholamine; Consummatory; Drinking; Locomotor activity; Stress; Ventral tegmental area