Comparative analysis of acute and chronic administration of haloperidol and clozapine using [3H] 2-deoxyglucose metabolic mapping.
In an effort to compare and contrast the mechanisms of action of typical and atypical antipsychotic drugs, [3H] 2-deoxyglucose metabolic mapping was employed following acute and chronic administration of haloperidol (1 mg/kg i.p. acute and 0.5 mg/kg i.p. chronic) and clozapine (20 mg/kg i.p., both acute and chronic). Optical density ratios (ODR) were measured in 62 brain structures. An overall decrease in ODR was observed in many of the regions analyzed. Acute haloperidol elicited significant decreases, particularly in the thalamus and hippocampus. Acute clozapine decreased glucose uptake in the caudate putamen, hippocampus, central gray, locus coreleus, and the thalamus. In both chronically treated haloperidol and clozapine animals, significant decreases in ODR were seen in the thalamus and hippocampal areas most dramatically, with other changes in the superior colliculus, retrospenial cortex, and the cerebellum. Clozapine caused significant effects in 32 nuclei acutely and only 19 nuclei chronically. Haloperidol caused significant effects in 23 nuclei acutely and 15 nuclei chronically. The pattern of change induced by haloperidol and clozapine were remarkably similar when considering their pharmacology is somewhat different. Both antipsychotics elicited fewer significant changes upon chronic administration.
CNS Pharmacology, Aventis Pharmaceuticals, 08807, Bridgewater, NJ, USA
Jill
J
Wotanis
Susan E
SE
Hanak
Joseph G
JG
Wettstein
Mark D
MD
Black
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D003024:Clozapine / Q000494:pharmacology*; D003847:Deoxyglucose; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008134:Long-Term Care; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D001786:Blood Glucose; D003847:Deoxyglucose; D003024:Clozapine; D006220:Haloperidol