Continuous oral olanzapine or clozapine treatment initiated in adolescence has differential short- and long-term impacts on antipsychotic sensitivity than those initiated in adulthood.

Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE

Publication: 2005- : Amsterdam : Elsevier Science
Original Publication: Amsterdam, North Holland Pub. Co.

Clozapine*/administration & dosage ; Clozapine*/pharmacology ; Olanzapine*/administration & dosage ; Antipsychotic Agents*/administration & dosage ; Antipsychotic Agents*/pharmacology ; Avoidance Learning*/drug effects; Animals ; Male ; Female ; Rats ; Administration, Oral ; Age Factors ; Time Factors ; Behavior, Animal/drug effects ; Benzodiazepines/administration & dosage ; Benzodiazepines/adverse effects ; Benzodiazepines/pharmacology ; Rats, Sprague-Dawley

One of the major discoveries in recent research on antipsychotic drugs is that antipsychotic treatment in adolescence could induce robust long-term alterations in antipsychotic sensitivity that persist into adulthood. These long-term impacts are likely influenced by various factors, including the "diseased" state of animals, sex, type of drugs, mode of drug administration, and age of treatment onset. In this study we compared the short- and long-term behavioral effects of 21-day continuous oral olanzapine (7.5 mg/kg/day) or clozapine (30.0 mg/kg/day) administration in heathy or maternal immune activated adolescent (33-53 days old) or adult (80-100 days old) rats of both sexes. We used a conditioned avoidance response model to assess the drug-induced alterations in antipsychotic sensitivity. Here, we report that while under the chronic drug treatment period, olanzapine progressively increased its suppression of avoidance responding over time, especially when treatment was initiated in adulthood. Clozapine's suppression depended on the age of drug exposure, with treatment initiated in adulthood showing a suppression while that initiated in adolescent did not. After a 17-day drug-free interval, in a drug challenge test, olanzapine treatment initiated in adolescence caused a decrease in drug sensitivity, as reflected by less avoidance suppression (a tolerance effect); whereas that initiated in adulthood appeared to cause an increase (more avoidance suppression, a sensitization effect). Clozapine treatments initiated in both adolescence and adulthood caused a similar tolerance effect. Our findings indicate that the same chronic antipsychotic treatment regimen initiated in adolescence or adulthood can have differential short- and long-term impacts on drug sensitivity.
Competing Interests: Declaration of competing interest The authors declare no conflict of interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

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R03 HD079870 United States HD NICHD NIH HHS

Keywords: Adolescent; Adult; Clozapine; Conditioned avoidance response; Maternal immune activation; Olanzapine

J60AR2IKIC (Clozapine)
N7U69T4SZR (Olanzapine)
0 (Antipsychotic Agents)
12794-10-4 (Benzodiazepines)

Date Created: 20240406 Date Completed: 20240426 Latest Revision: 20240527

20240527

PMC11128075

10.1016/j.ejphar.2024.176567

38582275