Microperfusion of 3-MPA into the brain augments GABA

•3-MPA steady-state concentrations were attained in the hippocampus and striatum via microdialysis.•Statistically significant increases in GABA concentrations occurred in both regions.•Marked elevations in glutamate were also documented in the hippocampus and striatum, and mechanisms for paradoxical GABA increases are proposed.•Effects of disinhibition are both model- and network activation level-dependent.

In vivo effects of microperfusion of a GABA synthesis inhibitor (3-MPA) into the striatum and hippocampus on amino acid concentrations and electrical neuronal activity were investigated.Paradoxical elevations in GABA in the striatum (5-fold in anesthetized and 50-fold in awake rats) and hippocampus (2-fold in anesthetized and 15-fold in awake rats) were documented under steady-state concentrations of 3-MPA along with expected increases in glutamate (a 15-fold increase and a 250-fold increase in the striatum of anesthetized and awake rats, respectively; a 7-fold increase and a 25-fold increase in the hippocampus of anesthetized and awake rats, respectively). There was no clear epileptiform or seizure activity.Explanations for the paradoxical increase in GABA are offered, and emphasis is placed on the dependency of disinhibition on the model in which its effects are studied as well as on the prevailing level of activation of the probed network.