Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters.

Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5--30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude. Smaller doses (less than 5 nA, 0.1 M solution or 20--50 nA, 20 mM in 0.16 M NaCl) reduced the excitation produced by glutamate, aspartate, and homocysteate, but antagonism of acetylcholine-evoked excitations required large flurazepam doses (up to 30 nA, 0.1 M solution). Even lower doses of flurazepam (less than 10 nA, 20 mM in 0.16 M NaCl) enhanced the inhibitory effect of gamma-aminobutyric acid (GABA) but antagonized that of 5-hydroxytryptamine, and had no effect on dopamine-induced inhibition of firing. Hence, only GABA-evoked inhibitions were significantly potentiated by flurazepam. These results demonstrate the multiple possible interactions between a benzodiazepine and different putative neurotransmitters in the mammalian cerebral cortex.