Lack of inhibition leads to abuse

Chronic drug use can lead to addiction, which is initiated by specific brain circuits. The mystery of how one class of drugs, the benzodiazepines, affects activity in this circuitry has finally been solved. Psychoactive benzodiazepines are widely used clinically and recreationally and although considered safe and effective in the short term, they are addictive in some individuals. All addictive drugs studied so far act to increase dopamine levels in the mesolimbic area of the brain and to trigger adaptive synaptic plasticity in the ventral tegmental area. A new study shows that benzodiazepines, which act by binding to GABAA receptors, also increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of α1-containing GABAA receptors in nearby interneurons. This in turn triggers drug-evoked synaptic plasticity in dopamine neurons. The data also suggest that subunit-selective benzodiazepines that do not activate α1 receptors may lack addictive properties.