Animal Models of Hallucinations: Continuous Stimulants

When amphetamine or cocaine is administered to humans every hour or so for several days, either during the “speed runs” of addicts or in controlled laboratory settings, there reliably results a psychosis that is similar to paranoid schizophrenia in a number of important aspects. This unique regimen of amphetamine intake, involving 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 or cocaine base. Monkeys and rats implanted with amphetamine pellets develop stages of behavioral alterations that are somewhat similar in sequence to those observed in humans who self-administer frequent doses of amphetamine. An initial period of hyperactivity and exploratory behavior is followed by the gradual development of motor stereotypies, then a period of relative inactivity, and finally, at three to five 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 behavior.Because continuous amphetamine administration also induces distinctive, neurotoxic alterations in dopaminergic innervations of the caudate nucleus, but not in mesolibic dopamine innervation of the nucleus accumbens or in several other neurotransmitte systems, we initially hypothesized that the hallucinatory behaviors were a reflection, in part, of the damaged caudate dopamine terminals.