Methysergide-induced precipitated withdrawal syndrome in phencyclidine-dependent rats

Chronic phencyclidine (PCP) administration has been shown to produce tolerance to a number of its pharmacological actions. We have suggested that PCP interacts with the 5-HT₂ receptors since it inhibits [³H]spiperone binding to 5-HT₂ receptors in vitro. In the present study, we investigated whether methysergide (a 5-HT₂ receptor blocker) induces the precipitated withdrawal syndrome in PCP-tolerant rats. The body weight of the rats in the abrupt and precipitated withdrawal groups was significantly lower 5 days and 1-5 days after withdrawal, respectively, than that in the control group. Furthermore, other typical precipitated abstinence syndrome characteristics such as jumping, wet-dog shake and ptosis were also observed in the precipitated withdrawal group. These results suggest that PCP produces its behavioral effects via an agonistic interaction with 5-HT₂ receptor sites and that our method may be very useful for the development of a rat model for studying physical dependence on PCP.