The neuropeptide, Org 5878 (desenkephalin-gamma-endorphin, DE gamma E), affects local cerebral glucose utilization in...

The effect of the antipsychotic peptide, Org 5878 (desenkephalin-gamma-endorphin, beta-endorphin-(6-17), on local cerebral glucose utilization was studied in freely moving male Wistar rats. Org 5878 (20 micrograms/kg, i.v.) or saline were given acutely and local cerebral glucose utilization was measured in 116 brain structures. Glucose uptake was not altered by Org 5878 in most brain areas, including areas of the nigrostriatal system, the cortex and the thalamus. However, significant reductions in glucose uptake were observed in the ventral tegmental area, the diagonal band complex, the hippocampus, the amygdala, the interpeduncular nucleus, the reticular nucleus of the thalamus and the cerebellum. These results indicate that the nigrostriatal and cortico-thalamic systems remain unaffected but the activity of the mesolimbic ventral tegmental area and of major target areas of cholinergic basal forebrain structures is selectively reduced following Org 5878 administration. It is concluded that the effect of Org 5878 on local cerebral glucose utilization is distinct from and more selective than that of antipsychotics currently used in the clinic.