Release of endogenous GABA from the substantia nigra is not controlled by GABA autoreceptors

Summary The characteristics of the release of GABA from slices of the rat substantia nigra, elicited by electrical stimulation at frequencies of 0.5–48 Hz and by elevated K⁺ concentrations ranging from 15–35 mmol/l, was studied. Comparisons were made with cortical slices where the data were not available from previous studies.No GABA release could be evoked from rat nigral slices by electrical stimulation between 0.5 and 4 Hz, in contrast to cortical slices, in which this pool is sensitive towards inhibition by (–)-baclofen. Also, comparatively less GABA release could be evoked from nigral than from cortical slices by K⁺ concentrations between 15 and 25 mmol/l. While (–)-baclofen at 10 mol/l inhibited release caused by 15 mol/l K⁺ in cortical, it did not in nigral slices. GABA release caused by higher frequencies (8–48 Hz) or 30 mmol/l K⁺ concentrations was Ca²⁺-dependent and in the former case also tetrodotoxin-sensitive. It had similar characteristics as in cortical slices and was insensitive towards (–)-baclofen, muscimol and bicuculline. Even more markedly than in the cortex, 30 mmol/l K⁺ released greater amounts of GABA than electrical stimulation at 24 Hz of a similar duration, suggesting the existence of one or several additional pool(s) of lesser excitability.Since the majority of gabaergic nerve endings in the nigra belong to striato- and pallidonigral projection neurons and those in the cortex probably exclusively to various types of interneurons, it seems that (a) one or several of the latter release GABA at low frequencies in a baclofen-sensitive manner and are absent or rare in the s. nigra, and (b) the striato- and pallidonigral projection neurons are not controlled by presynaptic autoreceptors of the GABA_A or GABA_B type, because neither GABA release elicited by electrical stimulation nor by 30 mmol/l K⁺ was affected by agents interfering with these types of receptors.Send offprint requests to P. C. Waldmeier at the above address