Effects of prolonged co-dergocrine mesylate (Hydergine) treatment on local cerebral glucose uptake in aged Fischer 344 rats.

Hydergine (co-dergocrine mesylate) was administered orally for 4 weeks to adult (10-12 months old) and aged (28 months old) Fischer 344 rats at dosages ranging from 0.1 mg to 4.0 mg/kg daily, in order to investigate its effect on 14C-deoxyglucose (DOG) uptake by the brain and the dose-effect relation. In the aged rats the dose-effect curve was bell-shaped, with maximal increases in DOG uptake at 0.6 mg/kg co-dergocrine. These were particularly pronounced in the caudoputamen (+47%), nucleus ventralis thalami (+32%), nucleus ventromedialis hypothalami (+57%) and the nucleus suprachiasmaticus (+39%), while the nucleus ambiguus, nucleus dorsalis nervi vagi, nucleus cuneatus and nucleus loci coeruleus also showed increases in DOG utilisation of between 23% and 29%. The dose-effect curve for the adult rats was similar in shape to that for the aged rats, but the peak was much lower and occurred at the lowest dosage (0.1 mg/kg). Cerebral DOG uptake responded considerably more sensitively in the adult rats than in the aged rats, so that the higher dosages were associated with a fall in DOG uptake. Parallels may be detected between the pharmacological effects exerted by co-dergocrine and its effects on DOG uptake in the nuclei of the extrapyramidal system (dopaminergic stimulation), in the hypothalamus (autonomic and neuroendocrine effects, regulation of body temperature and sleep) and in the alpha-receptor nuclei (alpha-blockade, cardiovascular regulation).