In both alcoholics and cocaine addicts compared with controls there was a near significant (FDR p = 0.050) down-regulation of SLC6A1 that encodes the principal neuronal GABA transporter (GAT1). Decreased levels of GAT1 could result in enhanced extracellular GABA levels, as has been shown to occur in GAT1 deficient mice [12]. Moreover, the effect of tiagabine, a GAT1 inhibitor is to reduce the subjective effects of cocaine in cocaine addicts [48]. This reduced response to drug or alcohol, i.e. ‘tolerance’, occurs with long-term use. Since there was no alteration in GAT1 expression in P rats, it is possible that the changes seen in humans may represent altered homeostasis seen in drug tolerance [49].
