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


Journal Article

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.

Full Text

Cited Authors

  • Davidson, C; Lazarus, C; Xiong, X; Lee, TH; Ellinwood, EH

Published Date

  • October 2002

Published In

Volume / Issue

  • 453 / 2-3

Start / End Page

  • 255 - 263

PubMed ID

  • 12398913

Pubmed Central ID

  • 12398913

Electronic International Standard Serial Number (EISSN)

  • 1879-0712

International Standard Serial Number (ISSN)

  • 0014-2999

Digital Object Identifier (DOI)

  • 10.1016/s0014-2999(02)02390-7


  • eng