Phencyclidine-induced head-twitch response in rats treated chronically with methysergide

Toshitaka Nabeshima, Kazuhiro Ishikawa, Kazumasa Yamaguchi, Hiroshi Furukawa, Tsutomu Kameyama

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10 Citations (Scopus)


This study was designed to assess whether phenycyclidine (PCP)-induced behaviors in rats were potentiated after two days' withdrawal from chronic methysergide (a 5-HT2 receptor blocker) treatment (10 mg/kg per day i.p. for 12 days), in order to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions. The PCP (10 mg/kg)-induced behaviors (head-twitch, head-weaving, turning and backpedalling) were attenuated by successive pretreatment with PCP (10 mg/kg per day i.p. for 12 days), while PCP- and 5-methoxy-N,N-dimethyltryptamine (2 mg/kg)-induced head-twitch increased significantly after the repeated methysergide treatment was stopped. The development of tolerance to PCP-induced head-twitch was antagonized by pretreatment with methysergide. Furthermore, Scatchard plots of specific [3H]ketanserin binding at the 5-HT2 receptors and [3H]PCP binding at the PCP receptors in the methysergide group revealed significant increases in binding capacity (Bmax) with no change in affinity (Kd). On the contrary, after development of tolerance to PCP, there were significant decreases in Bmax of [3H]ketanserin binding with no change in affinity. PCP can thus place [3H]ketanserin at the 5-HT2 receptor site, but not [3H]5-HT at the 5-HT1 receptor site. These facts indicate that PCP may produce head-twitch via an agonistic interaction with 5-HT2 receptor sites.

Original languageEnglish
Pages (from-to)319-328
Number of pages10
JournalEuropean Journal of Pharmacology
Issue number3
Publication statusPublished - 20-01-1987
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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