Pharmacology of cortical inhibition

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Abstract
The authors studied the effects of various pharmacological agents on the cortical inhibitory process described in the previous 2 papers (Krnjevi, Randi and Straughan, 1966); the drugs were mostly administered directly by iontophoresis from micro-pipettes and by systemic intravenous injection. Strychnine given by iontophoresis or by the application of a strong solution to the cortical surface potentiated excitatory effects, but very large iontophoretic doses also depressed neuronal firing. Subconvulsive and even convulsive systemic doses had little or no effect at the cortical level. There was no evidence, with any method of application, that strychnine directly interferes with the inhibitory process. Tetanus toxin, obtained from 2 different sources and injected into the cortex 12-48 hr previously, also failed to block cortical inhibition selectively. As with strychnine, there was some evidence of increased responses to excitatory inputs. Other convulsant drugs which failed to block cortical inhibition included picrotoxin, pentamethylene tetrazole, thiosemi-carbazide, longchain [omega] -amino acids and morphine. The inhibition was not obviously affected by cholinomimetic agents or by antagonists of acetylcholine. [alpha]- and [beta]-antagonists of adrenergic transmission were also ineffective. Cortical inhibition was fully developed in the presence of several general anesthetics, including ether, Dial, pento-barbitone, Mg and chloralose. A temporary reduction in inhibition which is sometimes observed after systemic doses of pentobarbital, is probably secondary to a fall in blood pressure. Several central excitants such as amphetamine, caffeine and lobeline also failed to show any specific antagonistic action on cortical inhibition. In view of the possibility that GABA [gamma amino butyric acid] is the chemical agent mediating cortical inhibition, an attempt was made to find a selective antagonist of its depressant action on cortical neurones. None of the agents listed above, nor any other of the substances tested, were able to block this action. Cortical inhibition differs from spinal inhibition in its pharmacological properties; these observations are consistent with the possibility that GABA is the cortical inhibitory transmitter.