Phencyclidine and ketamine: comparison with the effect of cocaine on the noradrenergic neurones of the rat brain cortex.
In slices of rat occipital cortex, the influence of phencyclidine and ketamine on the accumulation of 3H-noradrenaline and the subsequent outflow of tritium was investigated, and was compared with the effect of cocaine.--All three drugs inhibited the accumulation of tritium during incubation of the slices with 3H-noradrenaline. Phencyclidine was slightly, whereas ketamine was much less effective than cocaine.--All three drugs accelerated the spontaneous outflow of tritium from slices preincubated with 3H-noradrenaline. The acceleration caused by low concentrations probably reflects an inhibition of the re-uptake of spontaneously released 3H-noradrenaline; in addition, high concentrations (10(-4) M phencyclidine, 3 X 10(-4)-10(-3) M cocaine and 10(-3)-3 X 10(-3) M ketamine) appear to release tritiated compounds from the neurones. The distance between uptake-inhibiting and releasing concentrations was much greater for cocaine than for phencyclidine and ketamine.--All three drugs enhanced the overflow of tritium evoked by electrical field stimulation. The increase probably reflects an inhibition of the re-uptake of released 3H-noradrenaline; in addition, phencyclidine appears to enhance the release of noradrenaline per pulse.--The actions of phencyclidine and ketamine on central noradrenergic neurones may contribute to the characteristic psychotropic side-effects of these general anaesthetics.