Lack of a strong influence of neuroleptic decanoates on dopaminergic and GABAergic functions

Data concerning the incidence of extrapyramidal symptoms and the development of the supersensitivity to dopamine after administration of depot neuroleptics are controversial. The aim of the study was to examine the influence of depot neuroleptics on the sensitivity of dopamine receptors and GABA nigral receptors. Haloperidol decanoate (30 or 60 mg/kg im) and fluphenazine decanoate (12.5 or 25 mg/kg im) were injected twice at a 15 day interval. These treatments induced weak but very long-lasting catalepsy (60-105 days depending on the neuroleptic and its dose). The only significant enhancement of the apomorphine (0.25 mg/kg sc) stereotypy was observed 135 days after the lower dose of haloperidol and 230 days after the lower dose of fluphenazine. Haloperidol decanoate (30 mg/kg) did not influence the number of contralateral rotations induced by muscimol (10 or 25 ng/0.5 microliter) injected into the substantia nigra pars reticulata 35, 55 and 135 days after the first injection. Present results indicate that the dopaminergic supersensitivity after administration of depot neuroleptics is weak and appears very late, and that haloperidol decanoate does not induce nigral supersensitivity to GABA. It is suggested that the depot neuroleptics might induce less extrapyramidal symptoms in the clinic than the daily neuroleptic treatment.