COMPARATIVE-STUDY OF DOPAMINE METABOLISM WITH LOCAL CEREBRAL GLUCOSE-UTILIZATION IN RAT-BRAIN FOLLOWING THE ADMINISTRATION OF HALOPERIDOL DECANOATE

The effects of haloperidol decanoate on dopamine (DA) metabolism in discrete regions of rat brain were investigated and compared with changes in local cerebral glucose utilization (LCGU). The concentration of DA and its metabolite, homovanillic acid, and the alpha-methyl-p-tyrosine (alpha-MT)-induced decline of DA were measured in 6 brain regions by a high-performance liquid chromatographic assay. LCGU in 26 brain regions were examined by [C-14]2-deoxy-D-glucose autoradiography. At 24-hr after intramuscular injection of haloperidol decanoate (60 mg eq/kg to haloperidol), the concentration of homovanillic acid in the prefrontal cortex, caudate-putamen, accumbens nucleus, lateral amygdala, and medial thalamus showed significant increase compared with control values. On day 21, the increase in these regions was significantly attenuated with no significant difference from the controls. Furthermore, chronic haloperidol rats showed alpha-MT-induced decline of DA to a similar extent in the control rats. LCGU on day 21 showed significant decrease in the parietal cortex, and a tendency toward decrease in the prefrontal cortex, lateral amygdala and medial thalamus compared with the controls. There was no significant change in LCGU in the caudate-putamen or accumbens nucleus. Chronic haloperidol would thus appear to affect energy metabolism mainly in the cortico-thalamo-limbic circuits, and this may not correspond well to presynaptic DA metabolism.