5-HT2 receptor antagonists given in the acute withdrawal from daily cocaine injections can reverse established sensitization.
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.
Davidson
Colin
C
Department of Psychiatry, Box 3870, Duke University Medical Center, Durham, NC 27710, USA.
Lazarus
Cindy
C
Xiong
Xueying
X
Lee
Tong H
TH
Ellinwood
Everett H
EH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003024:Clozapine / Q000494:pharmacology; D003042:Cocaine / Q000009:adverse effects*; D007267:Injections; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
D012702:Serotonin Antagonists; D008803:Mianserin; D007650:Ketanserin; D003042:Cocaine; D003024:Clozapine