Neurochemical Parameters in the Hyperresponsive Phase After a Single Dose of Neuroleptics to Mice

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 [ 3 H]haloperidol, [ 3 H]cis (Z)‐flupenthixol, [ 3 H]apomorphine, [ 3 H]dopamine, [ 3 H]propylbenzilylcholine mustard and [ 3 H]GABA to striatal membranes in vitro is equal to that of saline‐treated mice. Specific binding of [ 3 H]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 [ 3 H]teflutixol in the final binding assay 4 days after intraperitoneal injection of [ 3 H]teflutixol (5 mg/kg) were too small to influence the binding of [ 3 H]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.