Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004) that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004) and is also predictive of smoking status. The predisposition of non-alcohol exposed subjects to initiate binge drinking is controlled by neuroimmune signaling that includes an innately activated neuronal Toll-like receptor 4 (TLR4) signal. This signal also regulates cognitive impulsivity, a heritable trait that defines drug abuse initiation. However, the mechanism of signal activation, its function in dopaminergic (TH+) neurons within the reward circuitry implicated in drug-seeking behavior [viz. the ventral tegmental area (VTA)], and its contribution to nicotine co-abuse are still poorly understood. We report that the γ-aminobutyric acidA receptor (GABAAR) α2 subunit activates the TLR4 signal in neurons, culminating in the activation (phosphorylation/nuclear translocation) of cyclic AMP response element binding (CREB) but not NF-kB transcription factors and the upregulation of corticotropin-releasing factor (CRF) and tyrosine hydroxylase (TH). The signal is activated through α2/TLR4 interaction, as evidenced by co-immunoprecipitation, and it is present in the VTA from drug-untreated alcohol-preferring P rats. VTA infusion of neurotropic herpes simplex virus (HSV) vectors for α2 (pHSVsiLA2) or TLR4 (pHSVsiTLR4) but not scrambled (pHSVsiNC) siRNA inhibits signal activation and both binge alcohol drinking and nicotine sensitization, suggesting that the α2-activated TLR4 signal contributes to the regulation of both alcohol and nicotine abuse.
Pubmed ID: 29690521 RIS Download
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsThis polyclonal targets Phospho-PKA C (Thr197)
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on April 12,2023. Matlab code for two-factor (location and year) analysis-of-variance model for the calculation of climate anomalies, in which the reference interval is specified as the full length of the dataset. This scheme avoids the affects of shorter (e.g. 1961-1990) reference intervals on the temporal evolution of the spatial standard deviation of climate anomalies. Data files provided.
View all literature mentionsThis polyclonal targets C-terminal (416-424)
View all literature mentionsThis unknown targets Goat Mouse IgG (H L)-HRP Conjugate
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Beta Actin
View all literature mentionsThis monoclonal targets Human NFkB p65
View all literature mentionsThis polyclonal targets Phospho-PKA C (Thr197)
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal targets Rabbit CRF/CRH
View all literature mentionsThis monoclonal targets TLR4 (25)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentions