Antipsychotic-induced suppression of locomotion in juvenile, adolescent and adult rats.

Abstract:

:Schizophrenia is a serious psychiatric disorder that is most frequently treated with the administration of antipsychotics. Although onset of schizophrenia typically occurs in late adolescence, the majority of preclinical research on the behavioral effects of antipsychotics and their mechanism(s) of action has been conducted on adult male animals. In this study, the acute effects of haloperidol (0.03-0.3 mg/kg, i.p.) and clozapine (1-10 mg/kg, i.p.) on locomotor activity were examined in juvenile [postnatal day 22 (PN22)], adolescent (PN40), and adult (>PN70) rats of both sexes. Subsequently, in order to determine whether tolerance to the activity suppressive effects of these drugs would occur in adolescents, PN40 rats were dosed and assessed for an additional nine days. While all groups exhibited some degree of suppression following acute administration of both drugs, juvenile rats were considerably more sensitive to this effect. With sub-chronic administration during late adolescent development (PN40-PN49), tolerance failed to develop. These results emphasize the importance of age in pharmacological characterization of antipsychotics and suggest that pre-adolescents may have enhanced sensitivity to the motor effects of these drugs. Further, they suggest that, similar to adults, older adolescents may not develop tolerance to the activity suppression induced by these two antipsychotics.

journal_name

Eur J Pharmacol

authors

Wiley JL

doi

10.1016/j.ejphar.2007.09.010

subject

Has Abstract

pub_date

2008-01-14 00:00:00

pages

216-21

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(07)01032-1

journal_volume

578

pub_type

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