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 Pharmacoljournal_title
European journal of pharmacologyauthors
Wiley JLdoi
10.1016/j.ejphar.2007.09.010subject
Has Abstractpub_date
2008-01-14 00:00:00pages
216-21issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)01032-1journal_volume
578pub_type
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