Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice.

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Title:	Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice.
Authors:	Gleason, S. D., Shannon, Harlan E.
Source:	Psychopharmacology. 1997, Vol. 129 Issue 1, p79. 6p.
Subjects:	Phencyclidine, Schizophrenia, Olanzapine, Clozapine, Mice, Physiology, Drugs
Abstract:	Abstract In humans, phencyclidine (PCP) is known to produce a syndrome of behavioral effects which have many characteristics in common with schizophrenia. Therefore, antagonism of PCP effects might be evidence for antipsychotic efficacy of a compound. In the present studies, the effects of the D[sub 2]-like antagonist haloperidol, the mixed D[sub 2]-like/5-HT[sub 2] antagonists olanzapine and clozapine, and a series of 5-HT receptor subtype selective antagonists on the hyperlocomotion produced by PCP were evaluated in mice. PCP (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The D[sub 2]-like antagonist haloperidol produced a dose-related decrease in locomotor activity when administered alone, and blocked the hyperactivity effects of PCP over the same dose-range (minimal effective dose, MED = 0.3 mg/kg for both effects). In contrast, olanzapine and clozapine reversed the hyperlocomotion effects of PCP at doses (MED = 0.03 and 0.3 mg/kg, respectively) approximately 30- and 10-fold, respectively, below those that decreased activity when administered alone (MED = 1.0 and 3.0 mg/kg, respectively). The selective 5-HT[sub 2] antagonist LY53857 (0.3-3.0 mg/kg) administered alone had no effect on locomotor activity but reversed (MED = 0.1 mg/kg) the effects of PCP. Similarly, the selective 5-HT[sub 2A/2C] antagonist ritanserin (0.001-1.0 mg/kg) alone had no effect on locomotor activity, but reversed (MED = 0.01 mg/kg) the effects of PCP. The selective 5-HT[sub 2A] antagonists ketanserin (MED = 3.0 mg/kg) and MDL 100,907 (MED = 0.3 mg/kg) produced dose-related decreases in locomotor activity and ketanserin (MED = 0.1 mg/kg) and MDL 100,907 (MED = 0.003 mg/kg) reversed the effects of PCP. The selective 5-HT[sub 3] antagonist zatosetron (0.01-10 mg/kg) and the selective... [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

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Abstract:	Abstract In humans, phencyclidine (PCP) is known to produce a syndrome of behavioral effects which have many characteristics in common with schizophrenia. Therefore, antagonism of PCP effects might be evidence for antipsychotic efficacy of a compound. In the present studies, the effects of the D[sub 2]-like antagonist haloperidol, the mixed D[sub 2]-like/5-HT[sub 2] antagonists olanzapine and clozapine, and a series of 5-HT receptor subtype selective antagonists on the hyperlocomotion produced by PCP were evaluated in mice. PCP (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The D[sub 2]-like antagonist haloperidol produced a dose-related decrease in locomotor activity when administered alone, and blocked the hyperactivity effects of PCP over the same dose-range (minimal effective dose, MED = 0.3 mg/kg for both effects). In contrast, olanzapine and clozapine reversed the hyperlocomotion effects of PCP at doses (MED = 0.03 and 0.3 mg/kg, respectively) approximately 30- and 10-fold, respectively, below those that decreased activity when administered alone (MED = 1.0 and 3.0 mg/kg, respectively). The selective 5-HT[sub 2] antagonist LY53857 (0.3-3.0 mg/kg) administered alone had no effect on locomotor activity but reversed (MED = 0.1 mg/kg) the effects of PCP. Similarly, the selective 5-HT[sub 2A/2C] antagonist ritanserin (0.001-1.0 mg/kg) alone had no effect on locomotor activity, but reversed (MED = 0.01 mg/kg) the effects of PCP. The selective 5-HT[sub 2A] antagonists ketanserin (MED = 3.0 mg/kg) and MDL 100,907 (MED = 0.3 mg/kg) produced dose-related decreases in locomotor activity and ketanserin (MED = 0.1 mg/kg) and MDL 100,907 (MED = 0.003 mg/kg) reversed the effects of PCP. The selective 5-HT[sub 3] antagonist zatosetron (0.01-10 mg/kg) and the selective... [ABSTRACT FROM AUTHOR]
ISSN:	00333158
DOI:	10.1007/s002130050165