The effects of chlordiazepoxide on synaptic transmission and amino acid neurotransmitter release in slices of rat olfactory cortex.

The rat olfactory cortex slice has been used to investigate the effects of chlordiazepoxide on evoked field potentials and the release of endogenous amino acid neurotransmitters (aspartate, glutamate, GABA and possibly taurine) which accompany electrical stimulation of the lateral olfactory tract. When single, low frequency stimuli were employed, chlordiazepoxide (2 microM-1 mM) depressed the amplitude of the field potential correlate of the depolarizing actions of the lateral olfactory tract excitatory transmitter (aspartate?) although aspartate release was unaffected. The field potential correlate of GABA-mediated presynaptic inhibition (late N-wave) was also depressed in amplitude but low drug concentrations (between approximately 2 and 50 microM) increased its peak duration . Effects of chlordiazepoxide on evoked inhibition were analyzed by giving paired stimuli such that the second stimulus occurred during the field potentials evoked by the first stimulus. Chlordiazepoxide (1-20 microM) increased the depression in amplitudes of the presynaptic massed action potential and late N-wave evoked by the second of a pair of stimuli compared with those evoked by the first stimulus suggesting that presynaptic inhibition was potentiated. These effects of chlordiazepoxide were accompanied by a significant reduction in aspartate release from the lateral olfactory tract terminals. Moreover, the drug effects on presynaptic inhibition and aspartate release were antagonized by picrotoxin (5 microM). On the other hand, chlordiazepoxide (1-50 microM) had no significant effect on postsynaptic inhibition. The results are discussed in terms of both the sites (presynaptic or postsynaptic) and mechanisms of action of chlordiazepoxide.