RT Journal Article
SR Electronic
T1 Alcohol dependence activates ventral tegmental area projections to central amygdala in male mice and rats
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.02.365445
DO 10.1101/2020.11.02.365445
A1 Elizabeth M Avegno
A1 Chelsea R Kasten
A1 William B Snyder III
A1 Leslie K Kelley
A1 Thomas D Lobell
A1 Taylor J Templeton
A1 Michael Constans
A1 Tiffany A Wills
A1 Jason W Middleton
A1 Nicholas W Gilpin
YR 2020
UL http://biorxiv.org/content/early/2020/11/03/2020.11.02.365445.abstract
AB The neural adaptations that occur during the transition to alcohol dependence are not entirely understood, but may include a gradual recruitment of brain stress circuitry by mesolimbic reward circuitry that is activated during early stages of alcohol use. Here, we focused on dopaminergic and non-dopaminergic projections from the ventral tegmental area (VTA), important for mediating acute alcohol reinforcement, to the central nucleus of the amygdala (CeA), important for alcohol dependence-related negative affect and escalated alcohol drinking. The VTA projects directly to the CeA, but the functional relevance of this circuit is not fully established. Therefore, we combined retrograde and anterograde tracing, anatomical, and electrophysiological experiments in mice and rats to demonstrate that the CeA receives input from both dopaminergic and non-dopaminergic projection neurons primarily from the lateral VTA. We then used slice electrophysiology and fos immunohistochemistry to test the effects of alcohol dependence on activity and activation profiles of CeA-projecting neurons in the VTA. Our data indicate that alcohol dependence activates midbrain projections to the central amygdala, suggesting that VTA projections may trigger plasticity in the CeA during the transition to alcohol dependence and that this circuit may be involved in mediating behavioral dysregulation associated with alcohol dependence.Competing Interest StatementNWG owns shares in Glauser Life Sciences, Inc., a start-up company with interest in development of therapeutics for treatment of mental illness. All other authors declare no competing financial interests.