[Effect of haloperidol decanoate on the dopaminergic system in the rat brain]

The effect of haloperidol decanoate and haloperidol on the dopaminergic system in the rat brain was studied. Each rat was treated with either once daily ip injection of haloperidol (5 mg/kg) for 4 weeks or a single sc injection of haloperidol decanoate followed by once daily ip injection of saline for 4 weeks. Three weeks after cessations of injections, the levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in the striatum, limbic area and frontal cortex 4 hours after a single ip injection of haloperidol (1 mg/kg). The haloperidol decanoate-treated rats showed lower levels of DOPAC and/or HVA than the rats of the other two groups. The DA level was higher only in the limbic area of the rats treated with haloperidol decanoate than that of the rats treated with saline. There was no difference of the levels of DA and its metabolites between the saline and haloperidol-treated rats. These results indicate that the haloperidol decanoate-treated rats developed a tolerance to an acute effect of haloperidol on stimulation of DA turnover in the three areas examined, while the haloperidol-treated rats developed no tolerance under these experimental conditions. A single sc injection of haloperidol decanoate to rat is expected to produce a long lasting blocking of the central DAergic system for at least 7 weeks. Such a property of this drug appears favourable for the maintenance therapy of schizophrenia.