Neurochemical changes in the entopeduncular nucleus and increased oral behavior in rats treated subchronically with clozapine or haloperidol

The purpose of the present experiment was to test the possibility that atyp ical antipsychotics and classical antipsychotics differentially regulate sp ecific neurochemical processes within the entopeduncular nucleus. For these experiments, rats were administered clozapine (25 mg/kg), haloperidol(1 mg /kg), or Tween-80 (control) daily for 21 days. Dopamine D-1-receptor bindin g was assessed with in vitro receptor autoradiographic methods and the mRNA s corresponding to the two forms of glutamate decarboxylase (glutamate deca rboxylase-65 and glutamate decarboxylase-67) were analyzed using in situ hy bridization histochemical methods. In addition, vacuous chewing movements ( VCM) were measured throughout the drug administration period as a functiona l indicator of drug action and changes in striatal dopamine D-2-receptor bi nding were measured as a positive control for D-2-receptor antagonist prope rties of haloperidol and clozapine. In agreement with previous reports, hal operidol increased D-2-receptor binding throughout the striatum while cloza pine had a more limited impact on D-2-receptors. Behavioral analysis reveal ed that both haloperidol and clozapine enhanced the display of vacuous chew ing movements to a similar extent but with a different postinjection latenc y. In the entopeduncular nucleus, clozapine increased D-1-receptor binding compared to controls while haloperidol was without effect. With respect to the regulation of GAD mRNAs, haloperidol increased glutamate decarboxylase- 65 and glutamate decarboxylase-67 mRNA levels throughout the entopeduncular nucleus. The effects of clozapine were restricted to increases in glutamat e decarboxylase-65 mRNA. These studies show that clozapine and haloperidol, both of which increase the occurrence of VCM, differentially modulate the neurochemistry of the entopeduncular nucleus. Synapse 34:192-207, 1999, (C) 1999 Wiley-Liss, Inc.