Changes specific to cocaine addiction were the down-regulation of GAD1 and GAD2, genes that encode glutamic acid decarboxylase, the enzyme responsible for the majority of GABA synthesis from glutamate in the CNS. The fact that GAT1 deficient mice, although having enhanced extracellular GABA levels, show unaltered levels of GAD1 and VGAT [44], [50] suggests that this change in GAD1 expression in cocaine addicts is likely to be independent and not compensatory for increased synaptic GABA. It is of interest that GAD1 has also been shown to be down-regulated in the hippocampus of patients with schizophrenia and bipolar disorder [51].
