Sensitization to nicotine significantly decreases expression of GABA transporter GAT-1 in the medial prefrontal cortex.

This study investigated GABA signaling following induction of behavioural sensitization to nicotine. Rats were repeatedly injected with saline, nicotine or hexamethonium for 18 days and gene expression was measured with qPCR. Nicotine upregulated GABAA alpha1 subunit expression in the nucleus accumbens (p<0.05) while no changes were observed for GABAA alpha3, alpha4 or alpha5. In the medial prefrontal cortex, no change in expression of the GABAA subunits was observed. We found that nicotine significantly decreased expression of the transporter GAT-1/SLC6A1 (p<0.05) in the medial prefrontal cortex while the expression of the GAT-3/SLC6A11 (p<0.05) transporter was increased in the nucleus accumbens. This provides the first evidence of neuroadaptive changes in the GABA system after nicotine sensitization and the first demonstration of an effect on GAT-1 or GAT-3 transporters in the addiction field. The GAT-1 findings also provide evidence for an alternative theory of why most schizophrenic individuals also use tobacco products.