Amphetamine stereotyped behaviors induced

At the higher doses, several stages of stereotyped behaviors were seen. The transition from amphetamine-induced locomotion to locomotion associated with stereotyped side-to-side head movements was accompanied by a further reduction in firing rate. In those animals in which focused stereotypy was observed following this period of locomotion plus head movements, neurons showed a still further reduction in firing rate (figure 2). 

Metaphit administered ICV prior to PCP administered ICV antagonized PCP induction of stereotyped behavior and ataxia up to 5 days after metaphit pretreatment. The antagonism of the behavioral effects of PCP by metaphit was dose dependent as is shown in figure 4. Furthermore, this antagonism by metaphit is specific as metaphit pretreatment ICV did not antagonize amphetamine-induced stereotyped behavior and could be prevented by pretreating rats with PCP just prior to metaphit administration. These results indicate that acylation of PCP receptors results in decreased ability of PCP to induce stereotyped behavior. 

Inhibition of conditioned (but not unconditioned) avoidance behavior is one of the most predictive tests of antipsychotic action. Another is the inhibition of amphetamine- or apomorphine-induced stereotyped behavior. Other tests that may predict antipsychotic action are reduction of exploratory behavior without undue sedation, induction of a cataleptic state, inhibition of intracranial self-stimulation of reward areas, and prevention of apomorphine-induced vomiting. Most of these tests are difficult to relate to any model of clinical psychosis. 

Creese I, Iversen SD (1974) The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia 39 345-357. 

Members of the Amaryllidaceae have also shown activity against central nervous system diseases other than depression and memory loss. For irrstance, the aqueous extracts of C. giganteum bulbs prolonged the drrration of penobarital sleeping time in rats. It also reduced spontaneous motor activity, decreased the exploratory activity and attenuated amphetamine-induced stereotype behavior in mice. These results seem to be predictive of the central sedative properties of the extract and the possible application in anxiety conditiorrs (49). 

Suzuki and colleagues (1986, 1987) have tested the effects of altering methamphetamine p-hydroxylation in rats it appeared that inhibition enhanced the methamphetamine-induced stereotyped behavior. One might conjecture that an equivalent effect could occur in humans with inborn CYP2D6 deficiency if a toxic dose of methamphetamine were applied. Unfortunately, studies of animals do not necessarily help p-hydroxyamphetamine is the main metabolite of amphetamine in rats but not in human liver (see above), and most studies on brain metabolism have not been conducted in human tissue. 

PEA has a similar structure to amphetamine and is well known to increase locomotion and induce stereotyped behaviors like amphetamine at higher, supraphysiological doses [10, 11, 19]. It was shown that the psychomotor effect of PEA may involve cholinergic and glutamatergic pathways in the striatum. PEA increased acetylcholine release in the striatum. PEA-associated stimulation of acetylcholine release was mediated by AMPA-type glutamatergic receptors [31]. 

Antagonism of amphetamine- or apomorphlne-induced stereotyped behavior is another characteristic effect of the antipsychotics. Most data favor the hypothesis that drug-induced stereotyped behavior is the result of DA activity in the neostriatum. However, a comparison of the effects of lesions in the neostriatum or in the tuberculum olfactorlum upon DA- and apomorphlne-induced stereotyped behavior suggests that DA activity in the limbic forebraln may be Important for this drug effect in the rat. ... 

Possibly at odds with the hypothesis that drug-induced stereotyped behavior involves a DA mechanism are observations on the effects of some stimulants on the turnover of brain CA in the rat. -Amphetamine, aminorex and p-chloramphetamine at doses which increased motor activity, but did not Induce stereotypies, caused an increase in turnover of DA but not of ME. These results are difficult to Interpret, however, because phenmetrazine did not alter turnover of DA or NE at a dose that increased motor activity. ... 

A stereotyped compulsive behavior is induced both in humans and in laboratory animals by amphetamines. This provided the basis for a method that has been used to measure the action of drugs on amphetamine-sensitive centers of the brain. A lesion in the nigrostriatal bundle on one side of a rat brain was made by injection of a neurotoxic compound such as 6-hydroxydopamine. This caused degeneration of dopamine-containing neurons on one side of the brain. When rats that had been injured in this way were given amphetamines, they developed a compulsive rotational behavior. Administration of chlorpromazine and several other antipsychotic drugs neutralized this behavior and in direct proportion to the efficacy in clinical use, an observation that also supports the theory that schizophrenia involves overactivity of dopamine neurons. 

Several lines of evidence show that dopamine (DA) is implicated in the mediation of some obsessive-compulsive behavior. Animal studies demonstrate that high doses of various dopaminergic agents, such as amphetamine, bromocriptine, apomorphine, and L-DOPA, induce stereotyped movements in animals, which resemble compulsive behaviors in OCD patients. Increased dopaminergic neurotransmission may be responsible for this. Human studies consistently report that abuse of stimulants such... 

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