CRF-amplified neuronal TLR4/MCP-1 signaling regulates alcohol self-administration.
Harry L June, Juan Liu, Kaitlin T Warnock, Kimberly A Bell, Irina Balan, Dominique Bollino, Adam Puche, Laure Aurelian
Index: Neuropsychopharmacology 40(6) , 1549-59, (2015)
Full Text: HTML
Abstract
Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking. It has a 50-60% risk contribution from inherited susceptibility genes; however, their exact identity and function are still poorly understood. We report that alcohol-preferring P rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol self-administration. The signal was sustained during alcohol drinking by increased expression of corticotropin-releasing factor and its feedback regulation of TLR4 expression, likely contributing to the transition to alcohol dependence.
Related Compounds
Related Articles:
2014-08-01
[Mol. Plant 7(8) , 1365-83, (2014)]
Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium.
2014-12-11
[Oncogene 33(50) , 5688-96, (2014)]
Functional consequence of the MET-T1010I polymorphism in breast cancer.
2015-02-20
[Oncotarget 6(5) , 2604-14, (2015)]
Aptamer-based polyvalent ligands for regulated cell attachment on the hydrogel surface.
2015-04-13
[Biomacromolecules 16(4) , 1382-9, (2015)]
2015-04-01
[J. Pineal Res. 58(3) , 310-20, (2015)]