Diazepam increases GABA mediated inhibition in the olfactory cortex slice.

The effect of diazepam on inhibition has been examined using an in vitro preparation of the guinea-pig olfactory cortex. Diazepam (0.03-30 mumol/l) doubled the intensity and duration of the recurrent inhibitory conductance. Diazepam had no effect on single evoked excitatory post-synaptic potential (e.p.s.p.) nor any effects on the action potential or membrane electrical constants. Diazepam (0.003-100 mumol/l) also reduced the multisynaptic e.p.s.p. generated through a recurrent pathway directed at the soma when elicited during the time-course of the inhibitory conductance. Diazepam had a comparitively small effect on the monosynaptic e.p.s.p. generated on the distal dendrite. Pentobarbitone had a similar though more intense effect over a narrow concentration range (10-200 mumol/l). The inhibitory coductance is thought to be GABA-mediated. Diazepam doubled the potency of the GABA analogue, muscimol, when applied via the bathing solution, whereas a modest 50 mumol/l pentobarbitone increased muscimol potency by about four-fold. The mild but selective effect of diazepam contrasts with the more intense and general effects of pentobarbitone and supports the idea that these drugs act through different mechanisms at the GABA receptor/channel complex.