Schizophrenia & Mania – Psychostimulant-induced hyperactivity
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In humans, acute administration of psychostimulants such as PCP or amphetamine induces psychosis-like symptoms. Administration of PCP, NMDA antagonist MK-801 or d-amphetamine to rodents leads to similar symptoms manifested in the increase in locomotor (distance traveled and rearing) and stereotypic activity. Most antipsychotics normalize the hyperactivity and stereotypic behavior seen after administration of d- amphetamine or PCP/MK-801.
PCP- and MK-801-induced hyperlocomotion is reversed by atypical antipsychotics such as olanzapine and clozapine, but insensitive to the typical antipsychotic haloperidol.
1) PCP-induced hyperactivity
PCP, administered at 30 minutes, increases locomotor activity in C57 mice. This behavior is attenuated when mice are pretreated with atypical antipsychotic clozapine (1 mg/kg; i.p.)
Dose response for the effect of acute PCP administration on locomotor activity in Sprague Dawley rats.
In Sprague Dawley rats, the atypical antipsychotic risperidone (0.5 and 1 mg/kg; i.p.) attenuates PCP-induced hyperactivity, while also decreasing baseline activity.
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In C57 mice, the atypical antipsychotics clozapine (left, 1 and 3 mg/kg; i.p.) and olanzepine (right, 0.03 and 0.1 mg/kg; i.p.) attenuate PCP-induced hyperactivity, quantified as total distance traveled during the 60-minute test session following PCP administration.
Dose response for the effects of the atypical antipsychotic aripiprazole in C57 mice (left), and Sprague Dawley rats (right). Aripiprazole attenuates PCP-induced hyperactivity in both mice (3-30 mg/kg, i.p.) and rats (1 and 10 mg/kg; i.p.)
2) MK-801-induced hyperactivity
Acute administration of the NMDA receptor antagonist MK-801 induces hyperactivity in rodents. Antipsychotic agents, such as clozapine, attenuate MK-801-induced hyperactivity.
