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

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 (B_max) with no change in affinity (K_d). On the contrary, after development of tolerance to PCP, there were significant decreases in B_max 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.