EFFECTS OF ACRYLAMIDE ON THE CENTRAL NERVOUS SYSTEM OF THE CAT

¹ Department of Pharmacology, Cornell University Medical College, New York 21

The neurologic effects of acrylamide on the cat have been described and some of the neural loci of the intoxication elucidated. The nature of the syndrome depended upon the dose magnitude, rate of administration and the length of time during which the agent was given. Severe tonic-clonic convulsions and other signs of a diffuse central excitation were produced by lethal doses. The repeated or single administration of sublethal doses gave rise to a chronic and reversible intoxication. This was characterized by an ataxia and tremor which were identical to those of cerebellar asynergia. No other biological effects were apparent at the dose levels required to initiate this syndrome. Histological alterations in neural tissue have not been revealed.

The administration of convulsive doses to cats with specific neural ablations and transections revealed that the excitatory effect was exerted on the entire central neuraxis but with significant quantitative variations. The presence of the cerebral cortex was required for a maximal convulsive effect and the spinal cord was found to be particularly insensitive to the excitatory effects of acrylamide. On the other hand, observations on the same type of surgical preparations suggested that the primary site of action of the nonconvulsive dose was subcortical.

Electroencephalographic studies confirmed the diffuse nature of the excitatory action. The nonconvulsive dose produced a striking but reversible electrocortical response which resembled that invoked by stimulation of the brain stem reticular activating system. Further EEG experiments on cerveau isolé, encephale isolé and infracollicular decerebrate preparations clearly showed that the focus of this disturbance was subcortical.

On the basis of available anatomical and physiological information and the experimental data reported herein, the mesencephalic tegmentum has been proposed as the primary neural locus of chronic acrylamide intoxication.

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