title: Effects of repeated risperidone exposure on serotonin receptor subtypes in developing rats.
abstract: Risperidone is an atypical antipsychotic drug that is widely prescribed to young patients with different psychotic disorders. The long-term effects of this antipsychotic agent on neuronal receptors in developing brain remain unclear and require further investigation. In this study, we examined the effects of long-term treatment of risperidone on two serotonin receptor subtypes in brain regions of juvenile rat. Levels of 5-HT(1A) and 5-HT(2A) receptors in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0mg/kg). Findings were compared to previously reported changes in 5-HT receptors after risperidone treatment (3.0mg/kg) in adult rat brain. The three doses of risperidone selectively and dose-dependently increased levels of 5-HT(1A) receptors in medial-prefrontal and dorsolateral-frontal cortices of juvenile animals. The higher doses (1.0 and 3.0mg/kg) of risperidone also increased 5-HT(1A) receptor binding in hippocampal CA(1) region of juvenile but not adult rats. In contrast, the three doses of risperidone significantly reduced 5-HT(2A) labeling in medial-prefrontal and dorsolateral-frontal cortices in juvenile as well as in adult animals in an equipotent fashion. 5-HT(1A) and 5-HT(2A) receptors in other forebrain regions were not altered by repeated risperidone treatment. These findings indicate that there are differential effects of risperidone on 5-HT(1A) and 5-HT(2A) receptors in juvenile animals, and that the 5-HT system in developing animals is more sensitive than adults to the long-term effects of risperidone.
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA 02478, USA.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Choi
authors.forename: Taylor
authors.initials: T
authors.lastname: Moran-Gates
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Gardner
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D018967:Risperidone / Q000008:administration & dosage*; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D018967:Risperidone