Striatal volume changes in the rat following long-term administration of typical and atypical antipsychotic drugs.
Striatal enlargement has been consistently reported in schizophrenics receiving chronic neuroleptic treatment although the results following atypical antipsychotic treatment have been equivocal. In order to disentangle patient illness from a possible drug effect on brain structure, young adult rats were administered either haloperidol, risperidone, clozapine, olanzapine, or vehicle daily for four or eight months via drinking water. Significant increases in caudate-putamen volumes were seen in animals receiving either haloperidol or clozapine when compared with control animals following eight months of drug administration. Conversely, olanzapine-treated animals showed significant decreases in caudate-putamen volumes when compared with control animals after eight months of drug. Thus, converging evidence indicates that the neuroplastic response of the striatum following neuroleptic exposure causes volumetric increases, whereas atypical antipsychotics affect the basal ganglia differentially. The current data suggests that such differential responses may be due to both the pharmacological properties and the relative doses of the atypical agents.
Andersson
Candace
C
Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA. Candace_Andersson@med.unc.edu
Hamer
Robert M
RM
Lawler
Cindy P
CP
Mailman
Richard B
RB
Lieberman
Jeffrey A
JA
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000097:blood; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003024:Clozapine / Q000009:adverse effects / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000009:adverse effects / Q000097:blood; D006984:Hypertrophy / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011699:Putamen / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000009:adverse effects / Q000097:blood; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone