Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice.
Level 5 - mechanism / opinion, no new human data
Animal research with no human clinical data
PubMed 21266194 · doi:10.1016/j.bbi.2011.01.008
What was done
Mice from several strains (C57BL/6J, FVB, FVBxB6F1, and B6xNZBF1), as well as CD14 knockout mice, were treated with a single intraperitoneal dose of lipopolysaccharide (LPS; 1 mg/kg). Voluntary alcohol consumption was measured using a continuous two-bottle choice test starting either one week or one month after LPS administration and tracked over several months. The researchers also evaluated ethanol-conditioned taste aversion, conditioned place preference, and the electrophysiological firing rates of ventral tegmental area dopamine neurons.
What was found
The abstract reports no exact numerical values, effect sizes, or confidence intervals. Directionally, LPS produced prolonged increases in voluntary alcohol consumption in C57BL/6J, FVBxB6F1, and B6xNZBF1 mice, but not in FVB inbred mice. Mice lacking CD14 exhibited no increase in alcohol intake following LPS treatment. In B6xNZBF1 mice, LPS treatment decreased ethanol-conditioned taste aversion without affecting conditioned place preference. Additionally, LPS pretreatment decreased the firing rate of dopamine neurons in the ventral tegmental area.
Why it matters
The study provides preclinical mechanistic evidence that transient innate immune activation can induce sustained increases in alcohol drinking behavior via CD14/TLR4-mediated neuroimmune pathways and altered dopamine signaling.
Limits
Findings are limited to mouse models, and translational relevance to human alcohol use disorder remains unverified. The abstract does not disclose sample sizes, exact drinking volumes, or statistical metrics. The effect of LPS was strain-dependent, and only a single dose of LPS (1 mg/kg) was evaluated.
Cited by
- supports Injecting lipopolysaccharide (LPS) into mice increases alcohol consumption and prevents alcohol-conditioned taste aversion, with the increased alcohol consumption lasting nearly 3 months in one study.