Brain c-aminobutyric acid: a neglected role in impulsivity

The investigation of impulsivity as a core marker of several major neuropsychiatric disorders has been greatly influenced by the therapeutic efficacy of drugs that block the reuptake of dopamine and noradrenaline in the brain. As a result, research into the neural mechanisms of impulsivity has focused on the catecholamine systems as the loci responsible for the expression of impul-sive behaviour and the primary mechanism of action of clinically effective drugs for attention-deficit hyperactivity disorder (ADHD). However, abnormalities in the catecholamine systems alone are unlikely to account for the full diversity and complexity of impul-sivity subtypes, nor can they fully explain co-morbid brain disorders such as drug addiction. Here we review the lesser-studied role of c-aminobutyric acid (GABA) in impulsivity, a major target of the dopaminergic and noradrenergic systems in the prefrontal cortex and striatum, and consider how abnormalities in this inhibitory neurotransmitter might contribute to several forms of impul-sive behaviour in humans and experimental animals. Our analysis reveals several promising leads for future research that may help inform the development of new therapies for disorders of impulse control