DOCOSAHEXAENOIC ACID REDUCES GABA RESPONSE IN SUBSTANTIA-NIGRA NEURONOF RAT

1. The effects of docosahexaenoic acid (DHA) on gamma-aminobutyric aci d (GABA) response (I-GABA) were investigated on the neuron acutely dis sociated from fat substantia nigra (SN), with the use of patch recordi ngs in a whole cell mode. 2. DHA (5 x 10(-6) M) reduced bicuculline-se nsitive GABA (10(-4) M) current by 50.3 +/- 13.1% (mean +/- SE) at a f ielding potential (V-h) Of -40 mV under voltage clamp. 3. The GABA con centrations for the half-maximum and threshold of I-GABA were not alte red by the presence or absence of 5 x 10(-6) M DHA in the external sol ution. 4. The decrease of 10(-4) M I-GABA, following the peak during G ABA application, was more rapid in the presence of 5 x 10 M DHA than i n its absence. The time constants for I-GABA decay were significantly different between the two conditions. 5. DHA reduced the I-GABA and th e glycine-induced response (I-gly) in a concentration-dependent manner . On the contrary, DHA potentiated the aspartate-induced response (I-a sp) in a concentration-dependent manner, suggesting that DHA influence s the activity of chloride channels but does not exhibit a nonspecific blocking effect on any ionic channel. 6. The application of thimerosa l did not affect the reduction of I-GABA by DHA, suggesting it unlikel y that DHA reduces the I-GABA by binding to phospholipids or triglycer ides and altering the lipid environment around the chloride channel. 7 . Arachidonic acid (AA) also reduced the I-GABA in a manner similar to DHA. Docosapentaenoic acid (DPA) reduced the I-GABA less potently tha n DHA. Other polyunsaturated and saturated fatty acids, such as docosa trienoic acid, docosatetraenoic acid, palmitic acid, and oleic acid, h ad very little or no effect on the I-GABA. 8. DHA, as well as AA, may play an important role in modulating neuronal excitability by reducing the I-GABA and I-gly, and potentiating N-methyl-D-aspartate receptor- mediated responses in the SN.