NEUROCHEMICAL PARAMETERS IN THE HYPERRESPONSIVE PHASE AFTER A SINGLE DOSE OF NEUROLEPTICS TO MICE

Abstract— Four days after a single dose of teflutixol (5 mg/kg i.p.), at which time mice are superresponsive to dopamine agonists, e.g. apomorphine, the specific binding of ³H]haloperidol, ³H]cis (Z)-flupenthixol, ³H]apomorphine, ³H]dopamine, ³H]propylbenzilylcholine mustard and ³H]GABA to striatal membranes in vitro is equal to that of saline-treated mice. Specific binding of ³H]haloperidol is also unchanged 3 days following a single dose of fluphenazine (5mg/kg i.p.) and 2 days following haloperidol (5 mg/kg i.p.), but slightly decreased 3 days following cis(Z)-flupenthixol (5 mg/kg i.p.).
The possibility that remaining neuroleptic or active metabolites could obscure a slight increase in dopamine receptor binding was rejected, since remaining amounts of ³H]teflutixol in the final binding assay 4 days after intraperitoneal injection of ³H]teflutixol (5 mg/kg) were too small to influence the binding of ³H]haloperidol in vitro .
It is concluded that the pharmacological superresponsiveness and the decrease in dopamine synthesis and release seen after the initial receptor blockade following a single dose of neuroleptic drugs in mice are nor accompanied by changes in dopamine, muscarine or GABAergic receptor characteristics in corpus striatum. The possibility that changes occur in a small number of functional operative dopamine receptors cannot be excluded, however.