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.
D000818:Animals; D008297:Male; D008784:Methysergide / Q000494:pharmacology*; D010622:Phencyclidine; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000503:physiopathology*
D011985:Receptors, Serotonin; D010622:Phencyclidine; D008784:Methysergide