The effect of ketotifen in rodent models of anxiety and on the behavioural consequences of withdrawing from treatment with drugs of abuse.
Ketotifen was compared to diazepam to inhibit aversive responding of the mouse in a black and white test box and in the rat social interaction test. Both drugs reduced aversive responding in the mouse to the brightly illuminated area of the test box and facilitated social interaction in the rat; ketotifen was approximately 100 times more potent than diazepam. The chronic administration of diazepam, ethanol, nicotine and cocaine in the mouse also reduced aversive responding but their withdrawal was associated with an increased behavioural suppression. The administration of ketotifen during the period of withdrawal from diazepam, ethanol, nicotine and cocaine prevented the exacerbation in aversive responding. It is concluded that ketotifen, like diazepam and 5-HT3 receptor antagonists, can reduce behavioural suppression in rodent models of anxiety and attenuate the behavioural consequences of withdrawal from treatment with drugs of abuse.
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, UK.
Kelly
M E
ME
Onaivi
E S
ES
Naylor
R J
RJ
D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D019966:Substance-Related Disorders / Q000523:psychology*
D000431:Ethanol; D009538:Nicotine; D003042:Cocaine; D003975:Diazepam; D007665:Ketotifen