title: Adult response to olanzapine or clozapine treatment is altered by adolescent antipsychotic exposure: a preclinical test in the phencyclidine hyperlocomotion model.
abstract: This study examined how repeated olanzapine (OLZ) or clozapine (CLZ) treatment in adolescence alters sensitivity to the same drug in adulthood in the phencyclidine (PCP) hyperlocomotion model. Male adolescent Sprague-Dawley rats (postnatal day (P) 44-48) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10.0 or 20.0 mg/kg, sc) and tested in the PCP (3.2 mg/kg, sc)-induced hyperlocomotion model for five consecutive days. Then a challenge test with OLZ (0.5 mg/kg) or CLZ (5.0 mg/kg) was administered either during adolescence (~P 51) or after the rats matured into adults (~P 76 and 91). During adolescence, repeated OLZ or CLZ treatment produced a persistent inhibition of PCP-induced hyperlocomotion across the five test days. In the challenge test during adolescence, rats previously treated with OLZ did not show a significantly stronger inhibition of PCP-induced hyperlocomotion than those previously treated with vehicle (VEH). In contrast, those previously treated with CLZ showed a weaker inhibition than the VEH controls. When assessed in adulthood, the enhanced sensitivity to OLZ and the decreased sensitivity to CLZ were detected on ~P 76, even on ~P 91 in the case of OLZ. These findings suggest that adolescent OLZ or CLZ exposure can induce long-term alterations in antipsychotic response that persist into adulthood.
authors.affiliation: 1Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shu
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010622:Phencyclidine; D003024:Clozapine; D000077152:Olanzapine
keywords: Olanzapine; adolescent drug treatment; clozapine; motor activity; phencyclidine; prepulse inhibition; sensitization; tolerance