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Neurochemical changes in the entopeduncular nucleus and increased oral behavior in rats treated subchronically with clozapine or haloperidol
Author(s) -
Yu Jiang,
Källström Lillemor,
Wiesel FritsAxel,
Johnson Allan E.
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(19991201)34:3<192::aid-syn4>3.0.co;2-l
Subject(s) - haloperidol , clozapine , neurochemical , pharmacology , glutamate decarboxylase , dopamine receptor d2 , glutamate receptor , chemistry , dopamine , striatum , medicine , endocrinology , psychology , receptor , schizophrenia (object oriented programming) , biochemistry , psychiatry , enzyme
Abstract The purpose of the present experiment was to test the possibility that atypical antipsychotics and classical antipsychotics differentially regulate specific 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 binding was assessed with in vitro receptor autoradiographic methods and the mRNAs corresponding to the two forms of glutamate decarboxylase (glutamate decarboxylase‐65 and glutamate decarboxylase‐67) were analyzed using in situ hybridization histochemical methods. In addition, vacuous chewing movements (VCM) were measured throughout the drug administration period as a functional indicator of drug action and changes in striatal dopamine D 2 ‐receptor binding were measured as a positive control for D 2 ‐receptor antagonist properties of haloperidol and clozapine. In agreement with previous reports, haloperidol increased D 2 ‐receptor binding throughout the striatum while clozapine had a more limited impact on D 2 ‐receptors. Behavioral analysis revealed that both haloperidol and clozapine enhanced the display of vacuous chewing movements to a similar extent but with a different postinjection latency. 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 glutamate 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. © 1999 Wiley‐Liss, Inc.