NEUROCHEMICAL PARAMETERS IN THE HYPER-RESPONSIVE 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. Copyright © 1979, Wiley Blackwell. All rights reserved