Intracerebral injection of gamma-vinyl-GABA: method for measuring rates of GABA synthesis in specific brain regions in vivo.

In order to obtain an index of the rate of GABA synthesis in different rat brain regions, we examined the rate of accumulation of GABA after irreversible inhibition of GABA-transaminase. Gamma-vinyl-GABA (GVG), a catalytic inhibitor of GABA-transaminase, was microinjected directly into each of four brain areas: superior colliculus (SC), substantia nigra (SN), frontal cortex (CTX) and caudate-putamen (CP). The subsequent rate of GABA accumulation was linear for at least 90 min in all regions, and was found to be 2-3 times higher in the SC and SN than in the CTX and CP. The nerve terminal contribution to the initial rate of GABA accumulation after GVG was determined by comparing values obtained in the intact SN with those obtained in the SN in which the GABAergic afferent terminals had been destroyed. The initial rate of GABA accumulation in the denervated SN was less than one-half of that measured in the intact SN, indicating that, under normal conditions, both nerve-terminal and non-nerve-terminal (perikarya, glia) compartments contribute to the rate of GABA accumulation after GABA-transaminase inhibition. Our results indicate that the intracerebral injection of GVG is a sensitive and reliable method for studying in vivo GABA synthesis in brain. Although the rate of GABA accumulation after GVG is sensitive to changes in the nerve terminal compartment, other GABA compartments may also influence these measurements.