5-HT2 receptor antagonists given in the acute withdrawal from daily cocaine injections can reverse established sensitization

Eur J Pharmacol. 2002 Oct 25;453(2-3):255-63. doi: 10.1016/s0014-2999(02)02390-7.


Male Sprague-Dawley rats were given two separate sensitizing regimens of cocaine (7 days on, 7 days off, 7 days on at 40 mg/kg/day, s.c.) or saline injections. Half of the animals also received a drug with 5-hydroxytryptamine-2 (5-HT2) receptor antagonist properties (clozapine, 3 mg/kg; mianserin 6 mg/kg; ketanserin 1 mg/kg, all s.c.) or saline during the second cocaine dosing regimen in the acute withdrawal period, 3.5 h after each cocaine injection. On day 10 of withdrawal animals were challenged with cocaine (7.5 mg/kg, i.p.) and assessed by a behavioral rating scale and locomotor activity monitoring. The 5-HT2 receptor antagonists, but not saline, reversed behavioral sensitization and had little effect on behavior in the control animals. 5-HT2 receptor antagonists, therefore, may be a useful treatment for cocaine addicts that have undergone previous sensitization periods. The pharmacological profile of these antagonists suggests that the 5-HT2A receptor subtype may mediate this effect.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Clozapine / pharmacology
  • Cocaine / adverse effects*
  • Injections
  • Ketanserin / pharmacology
  • Male
  • Mianserin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / pharmacology*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / psychology


  • Serotonin Antagonists
  • Mianserin
  • Ketanserin
  • Cocaine
  • Clozapine