Haloperidol (but not ziprasidone) withdrawal enhances cocaine-induced locomotor activation and conditioned place preference in mice.
It has been empirically suggested that the high incidence of drug abuse in schizophrenic patients is related to chronic neuroleptic treatment. We investigated the effects of withdrawal from long-term administration of the typical neuroleptic haloperidol and/or the atypical agent ziprasidone on the acute locomotor stimulant effect of cocaine as well as on cocaine-induced conditioned place preference (CPP). In the first experiment, mice were i.p. treated with haloperidol (1.0 mg/kg) and/or ziprasidone (4.0 mg/kg) for 15 days. At 72 h after the last injection, animals received an i.p. injection of cocaine (10 mg/kg) and their locomotor activity was quantified. In the second experiment, mice were withdrawn from the same haloperidol or ziprasidone treatment schedule and submitted to CPP. Withdrawal from haloperidol (but not ziprasidone or ziprasidone plus haloperidol) increased both cocaine-induced hyperactivity and CPP. These findings indicate that withdrawal from long-term treatment with typical neuroleptic drugs such as haloperidol (but not the atypical compound ziprasidone) may enhance some behavioral effects of cocaine in mice which have been related to drug dependence in humans.
Fukushiro
Daniela Fukue
DF
Department of Pharmacology, Universidade Federal de São Paulo, R. Botucatu, 862, Ed. Leal Prado, 10 andar, 04023062, São Paulo, SP, Brazil. danifukushiro@gmail.com
Alvarez
Juliana do Nascimento
Jdo N
Tatsu
Julie Anne Obara
JA
de Castro
Juliana Pedroso Moraes Vilela
JP
Chinen
Cibele Cristina
CC
Frussa-Filho
Roberto
R
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D006220:Haloperidol