Phencyclidine-induced head-twitch response in rats treated chronically with methysergide.
T Nabeshima, K Ishikawa, K Yamaguchi, H Furukawa, T Kameyama
European journal of pharmacology January 20, 1987 DOI: 10.1016/0014-2999(87)90028-8
Summary
PCP-induced head-twitch behavior significantly increased after a two-day withdrawal from chronic methysergide treatment (10 mg/kg daily for 12 days). In a sample of rats, PCP (10 mg/kg) led to reduced head-twitch behaviors during treatment, while withdrawal resulted in heightened responses. Notably, pretreatment with methysergide prevented tolerance to these behaviors. Binding studies revealed that methysergide increased the capacity of 5-HT2 receptors, indicating that PCP interacts agonistically at these sites, which may explain its effects on head-twitch behavior.
Abstract
This study was designed to assess whether phencyclidine (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 displace [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.