title: Repeated aripiprazole treatment causes dopamine D2 receptor up-regulation and dopamine supersensitivity in young rats.
abstract: Aripiprazole is a second-generation antipsychotic that is increasingly being prescribed to children and adolescents. Despite this trend, little preclinical research has been done on the neural and behavioral actions of aripiprazole during early development. In the present study, young male and female Sprague-Dawley rats were pretreated with vehicle, haloperidol (1 mg/kg), or aripiprazole (10 mg/kg) once daily on postnatal days (PD) 10-20. After 1, 4, or 8 days (i.e. on PD 21, PD 24, or PD 28), amphetamine-induced locomotor activity and stereotypy, as well as dorsal striatal D2 receptor levels, were measured in separate groups of rats. Pretreating young rats with aripiprazole or haloperidol increased D2 binding sites in the dorsal striatum. Consistent with these results, dopamine supersensitivity was apparent when aripiprazole- and haloperidol-pretreated rats were given a test day injection of amphetamine (2 or 4 mg/kg). Increased D2 receptor levels and altered behavioral responding persisted for at least 8 days after conclusion of the pretreatment regimen. Contrary to what has been reported in adults, repeated aripiprazole treatment caused D2 receptor up-regulation and persistent alterations of amphetamine-induced behavior in young rats. These findings are consistent with human clinical studies showing that children and adolescents are more prone than adults to aripiprazole-induced side effects, including extrapyramidal symptoms.
authors.affiliation: 1Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Fausto A
authors.initials: FA
authors.lastname: Varela
authors.forename: Taleen
authors.initials: T
authors.lastname: Der-Ghazarian
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Sergios
authors.initials: S
authors.lastname: Charntikov
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Crawford
authors.forename: Sanders A
authors.initials: SA
authors.lastname: McDougall
mesh_terms: D000367:Age Factors; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000068180:Aripiprazole; D001665:Binding Sites / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine
keywords:  d-amphetamine; Aripiprazole; haloperidol; ontogeny; receptor up-regulation; supersensitivity
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