title: Early Antipsychotic Treatment in Juvenile Rats Elicits Long-Term Alterations to the Dopamine Neurotransmitter System.
abstract: Prescription of antipsychotic drugs (APDs) to children has substantially increased in recent years. Whilst current investigations into potential long-term effects have uncovered some alterations to adult behaviours, further investigations into potential changes to neurotransmitter systems are required. The current study investigated potential long-term changes to the adult dopamine (DA) system following aripiprazole, olanzapine and risperidone treatment in female and male juvenile rats. Levels of tyrosine hydroxylase (TH), phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D₁ and D₂ receptors were measured via Western blot and/or receptor autoradiography. Aripiprazole decreased TH and D₁ receptor levels in the ventral tegmental area (VTA) and p-TH levels in the prefrontal cortex (PFC) of females, whilst TH levels decreased in the PFC of males. Olanzapine decreased PFC p-TH levels and increased D₂ receptor expression in the PFC and nucleus accumbens (NAc) in females only. Additionally, risperidone treatment increased D₁ receptor levels in the hippocampus of females, whilst, in males, p-TH levels increased in the PFC and hippocampus, D₁ receptor expression decreased in the NAc, and DAT levels decreased in the caudate putamen (CPu), and elevated in the VTA. These results suggest that early treatment with various APDs can cause different long-term alterations in the adult brain, across both treatment groups and genders.
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. mds953@uowmail.edu.au.|School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia. mds953@uowmail.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. jl841@uowmail.edu.au.|School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia. jl841@uowmail.edu.au.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lian
authors.affiliation: School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia. xhuang@uow.edu.au.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. chao@uow.edu.au.|School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia. chao@uow.edu.au.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000068180:Aripiprazole / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D000068180:Aripiprazole; D014446:Tyrosine 3-Monooxygenase; D018967:Risperidone; D000077152:Olanzapine; D004298:Dopamine
keywords: antipsychotic; aripiprazole; development; dopamine; juvenile; olanzapine; risperidone