Measurement of GABA using J-difference edited (1) H-MRS following modulation of synaptic GABA concentration with tiagabine.

Synapse (New York, N.Y.)

PubMedID: 24756906

Myers JF, Evans CJ, Kalk NJ, Edden RA, Lingford-Hughes AR. Measurement of GABA using J-difference edited (1) H-MRS following modulation of synaptic GABA concentration with tiagabine. Synapse. 2014;.
Though GABA is the major inhibitory neurotransmitter in the brain, involved in a wide variety of brain functions and many neuropsychiatric disorders, its intracellular and metabolic presence provides uncertainty in the interpretation of the GABA signal measured by (1) H-MRS. Previous studies demonstrating the sensitivity of this technique to pharmacological manipulations of GABA have used non-specific challenges that make it difficult to infer the exact source of the changes. In this study, the synaptic GABA reuptake inhibitor tiagabine, which selectively blocks GAT1, was used to test the sensitivity of J-difference edited (1) H-MRS to changes in extracellular GABA concentrations. MEGA-PRESS was used to obtain GABA-edited spectra in 10 male individuals, before and after a 15 mg oral dose of tiagabine. In the three voxels measured, no significant changes were found in GABA+ concentration after the challenge compared to baseline. This dose of tiagabine is known to modulate synaptic GABA and neurotransmission through studies using other imaging modalities, and significant increases in self-reported sleepiness scales were observed. Therefore it is concluded that recompartmentalisation of GABA through transport block does not have a significant impact on total GABA concentration. Furthermore, it is likely that the majority of the MRS-derived GABA signal is intracellular. It should be considered, in individual interpretation of GABA MRS studies, whether it is appropriate to attribute observed effects to changes in neurotransmission. Synapse, 2014. © 2014 Wiley Periodicals, Inc.