Continuous amphetamine intoxication: an animal model of the acute psychotic episode

When amphetamines are administered to humans every few hours for several days, either during the 'speed runs' of addicts or in controlled laboratory settings, the psychosis which reliably results is similar to paranoid schizophrenia in a number of important aspects. This unique regimen of drug intake, which involves the continuous presence of stimulants over a prolonged period of time, can be simulated in animals using subcutaneously implanted slow-release silicone pellets containing d-amphetamine base. Monkeys and rats implanted with these pellets develop stages of behavioural alterations which are somewhat similar in sequence to those observed in humans who have received frequent doses of amphetamine. An initial period of hyperactivity and exploratory behaviour is followed by the gradual development of motor stereotypies which become virtually incessant. A period of relative inactivity then appears which is followed, at 4-5 days after pellet implantation, by a late stage. This final stage is characterized by 'wet-dog' shakes, parasitotic-like grooming episodes, and a variety of other forms of hallucinatory-like behaviour. At about the same time there are distinctive and partially irreversible alterations in dopaminergic innervations of the caudate nucleus, but not in mesolimbic dopamine innervation of the nucleus accumbens or in several other neurotransmitter systems. Continuous amphetamine administration may reproduce some aspects of the prolonged excitation which accompanies an acute psychotic episode and may be a fruitful model for the clarification of the dopamine theory of schizophrenia.