Effects of risperidone on dopamine receptor subtypes in developing rat brain.
The atypical antipsychotic risperidone is often prescribed to pediatric patients with neuropsychiatric disorders, though its effects on the developing brain remain unclear. Accordingly, we studied the effects of repeated treatment of risperidone on dopamine receptors in brain regions of juvenile rat. Levels of dopamine receptors (D(1), D(2), D(3), D(4)) in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0 mg/kg/day) increased levels of D(1) receptors in nucleus accumbens and caudate-putamen of juvenile, but not adult rats. Conversely, all three doses of risperidone dose-dependently increased D(2) labeling in medial prefrontal cortex and hippocampus, and D(4) receptor in nucleus accumbens, caudate-putamen and hippocampus of juvenile animals as well as in adults. Only the high dose of risperidone (3.0 mg/kg) increased D(2) receptors in caudate-putamen in both juvenile and adult brain. D(3) receptors were not altered by risperidone in any brain region at any dose or age. The findings indicate dose-dependent effects of risperidone on dopamine receptors in developing animals, and that juvenile animals are more sensitive than adults to the cerebral effects of risperidone.
Moran-Gates
Taylor
T
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA.
Grady
Christopher
C
Shik Park
Young
Y
Baldessarini
Ross J
RJ
Tarazi
Frank I
FI
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology*
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D018967:Risperidone