Risperidone prevents the development of supersensitivity, but not tolerance, to phencyclidine in rats treated with subacute phencyclidine

Kiyoyuki Kitaichi, Kiyofumi Yamada, Yukio Yoneda, Kiyokazu Ogita, Takaaki Hasegawa, Hiroshi Furukawa, Toshitaka Nabeshima

研究成果: Article

21 引用 (Scopus)

抜粋

We investigated whether risperidone, a 5-HT2/dopamine-D2 receptor antagonist, inhibits the development of tolerance and supersensitivity to PCP and whether subacute administration of PCP with risperidone affects the [3H]MK-801 binding in rat brain, in comparison with dopamine-D2 receptor antagonist haloperidol and 5-HT2 receptor antagonist ritanserin. In rats treated with PCP (10 mg/Kg, I.p.) for 14 days, PCP (10 mg/Kg, I.p.)-induced hyperlocomotion, rearing and sniffing were potentiated (supersensitivity), and head-weaving, head-twitch, backpedalling and turning were diminished (tolerance). The development of supersensitivity to PCP was blocked by oral co-administration of risperidone (2.4 mg/Kg, P.o.) and haloperidol (1.0 mg/Kg, P.o.) for 14 days, but not ritanserin (10 mg/Kg, P.o.) and risperidone (0.8 mg/Kg, P.o.), while no drugs prevented the development of tolerance to PCP. Both risperidone (2.4 mg/Kg, P.o.) and haloperidol (1.0 mg/kg, p.o.) also inhibited the cross-supersensitivity to methamphetamine (MAP; 2.5 mg/Kg, I.p.)-induced rearing in rats treated with PCP for 14 days. The profiles of [3H]MK-801 binding in discrete brain areas did not change after subacute administration of PCP alone or in combination with risperidone, haloperidol or ritanserin for 14 days. Therefore, it is suggested that subacute administration of PCP may cause functional changes in the dopaminergic neuronal transmission under conditions where the binding of [3H]MK-801 in discrete brain areas is unchanged, and that co-administration of risperidone may block these PCP-induced changes in neuronal function.

元の言語English
ページ(範囲)531-543
ページ数13
ジャーナルLife Sciences
56
発行部数7
DOI
出版物ステータスPublished - 06-01-1995
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

これを引用