Neuronal sensitivity to substance P is increased after repeated treatment with tranylcypromine, carbamazepine or oxaprotaline, but decreased after repeated electroconvulsive shock.

The responsiveness of neurones in the cingulate cortex of the rat to the excitatory effects of iontophoretically applied substance P (SP) was determined after chronic administration of several drugs known to possess antidepressant actions. The agents tested were tranylcypromine, carbamazepine and oxaprotiline [(+) and (-)isomers]. Twenty-four to 36 hr after the last of 14 consecutive daily treatments there was an increase in neuronal sensitivity to substance P with all three drugs. The two isomers of oxaprotaline were equally active in inducing this change in sensitivity. None of the agents significantly altered responses to substance P after a single acute treatment. Responsiveness to substance P was also tested one day after the last of 14 daily treatments with electroconvulsive shock. In this case there was a marked reduction of the sensitivity of cingulate neurones to substance P with no apparent change in responsiveness to acetylcholine. A single shock treatment did not detectably alter responses to substance P.