Antagonism of Methylphenidate‐Induced Stereotyped Gnawing in Mice

Abstract

Abstract: It was observed by chance that methylphenidate induces an intense stereotyped gnawing in mice. Amphetamine too, induces stereotyped behaviour in mice, but this behaviour is mainly characterized by licking and rapid movements of the head and forelegs. Thus, the behavioural effects of amphetamine and methylphenidate in mice seem to be different under certain experimental conditions. The effect of methylphenidate was not blocked by pretreatment with dopamine‐β‐hydroxylase inhibitors and phenoxybenzamine, while the dopamine receptor blocking neuroleptics caused a complete inhibition. These findings support the view that brain dopamine is associated with production of stereotyped behaviour. Pretreatment with the tyrosine hydroxylase inhibitor d,1‐α‐methyltyrosine methylester (H 44/68) 1, 2 or 3 hours before methylphenidate caused no or only partial inhibition of the stimulant effect. Pretreatment with H 44/68 5 hours before methylphenidate completely inhibited the development of compulsive gnawing, indicating that the antagonistic effect of H 44/68 seems to be correlated with gross depletion of catecholamines from the brain. Reserpine too, was found to inhibit the effect of methylphenidate. A series of centrally acting drugs were tested for antagonistic effect of methylphenidate and only the neuroleptics proved to be active. A classification of 20 neuroleptics with respect to their methylphenidate antagonistic effect is presented. The clinically potent neuroleptics were active in very low doses, but the weaker “basal” neuroleptics like chlorpromazine and thioridazine also showed a clearcut effect.