SUPERSENSITIVITY TO CENTRAL STIMULANT ACTIONS OF ADRENERGIC DRUGS FOLLOWING DISCONTINUATION OF A CHRONIC DIET OF ALPHA-METHYLTYROSINE

Spontaneous and amphetamine-stimulated locomotor activity were determined before, during and after a two week period in which mice were fed a diet containing 0.3% dl-α-methyltyrosine. After one day of the α-methyltyrosine diet both spontaneous and amphetamine-stimulated activity were depressed but tolerance to the depression developed by the thirteenth day of the diet. Both measures of activity were significantly higher than control (pre-diet) values one day after the diet was discontinued. Ephedrine-stimulated motor activity was also blocked after one day of the α-methyltyrosine diet and enhanced one day after cessation of the diet whereas the stimulant effects of pipradrol and methylphenidate were not significantly altered at these times. The central stimulant actions of only those drugs which have been shown to release endogenous catecholamines (amphetamine and ephedrine) are blocked by α-methyltyrosine and enhanced after a chronic diet of this drug is discontinued. It is proposed that the central excitation that follows cessation of chronic α-methyltyrosine administration is the result of an increase in the sensitivity of central adrenergic receptors. © 1969 Springer-Verlag.