Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat

.1. The effects of docosahexaenoic acid (DHA) on gamma-aminobutyric acid (GABA) response (IGABA) were investigated on the neuron acutely dissociated from rat substantia nigra (SN), with the use of patch recordings in a whole cell mode. 2. DHA (5 x 10(-6) M) reduced bicuculline-sensitive GABA (10(-4) M) current by 50.3 +/- 13.1% (mean +/- SE) at a holding potential (Vh) of -40 mV under voltage clamp. 3. The GABA concentrations for the half-maximum and threshold of IGABA were not altered by the presence or absence of 5 x 10(-6) M DHA in the external solution. 4. The decrease of 10(-4) M IGABA, following the peak during GABA application, was more rapid in the presence of 5 x 10(-6) M DHA than in its absence. The time constants for IGABA decay were significantly different between the two conditions. 5. DHA reduced the IGABA and the glycine-induced response (Igly) in a concentration-dependent manner. On the contrary, DHA potentiated the aspartate-induced response (Iasp) in a concentration-dependent manner, suggesting that DHA influences the activity of chloride channels but does not exhibit a nonspecific blocking effect on any ionic channel. 6. The application of thimerosal did not affect the reduction of IGABA by DHA, suggesting it unlikely that DHA reduces the IGABA by binding to phospholipids or triglycerides and altering the lipid environment around the chloride channel. 7. Arachidonic acid (AA) also reduced the IGABA in a manner similar to DHA. Docosapentaenoic acid (DPA) reduced the IGABA less potently than DHA. Other polyunsaturated and saturated fatty acids, such as docosatrienoic acid, docosatetraenoic acid, palmitic acid, and oleic acid, had very little or no effect on the IGABA. 8. DHA, as well as AA, may play an important role in modulating neuronal excitability by reducing the IGABA and Igly, and potentiating N-methyl-D-aspartate receptor-mediated responses in the SN.