Details

Autor(en) / Beteiligte

• Yu, Jiang
• Källström, Lillemor
• Wiesel, Frits-Axel
• Johnson, Allan E.

Titel

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

Ist Teil von

• Synapse (New York, N.Y.), 1999-12, Vol.34 (3), p.192-207

Ort / Verlag

New York: John Wiley & Sons, Inc

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 D1‐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 D2‐receptor binding were measured as a positive control for D2‐receptor antagonist properties of haloperidol and clozapine. In agreement with previous reports, haloperidol increased D2‐receptor binding throughout the striatum while clozapine had a more limited impact on D2‐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 D1‐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.