Methysergide-induced precipitated withdrawal syndrome in phencyclidine-dependent rats

Neurosci Lett. 1986 Sep 12;69(3):275-8. doi: 10.1016/0304-3940(86)90493-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Methysergide / pharmacology*
  • Phencyclidine*
  • Rats
  • Rats, Inbred F344
  • Receptors, Serotonin / drug effects*
  • Substance Withdrawal Syndrome / physiopathology*
  • Substance-Related Disorders / physiopathology*

Substances

  • Receptors, Serotonin
  • Phencyclidine
  • Methysergide