Effects of chronic haloperidol on vitamin E levels and monoamine metabolism in rats fed normal and vitamin E deficient diets.
Experiments were conducted to study the effects of chronic haloperidol treatment on brain catechols and indoles in rats fed vitamin E deficient diets. Rats were fed basal diet or vitamin E deficient diet and injected with saline or haloperidol (1 mg/kg/day x 28 days i.p.). Tissue levels of catechols, indoles and vitamin E were measured using HPLC-EC techniques. Chronic haloperidol reduced striatal vitamin E levels. Activity in the striatal dopaminergic systems was also reduced, as, shown by reduced 3,4-dihydrophenylanine (DOPA), homovanillic acid (HVA), 3-methoxytyramine (3-MT), and dopamine (DA) levels. In addition, serotonergic activity was reduced, as indicated by lowered 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), and 5-hydroxytryptamine (5-HT) levels. In the substantia nigra, only 5-HIAA levels were reduced by treatment with haloperidol. These effects of haloperidol on monoamine metabolism were noted in both the vitamin E deficient and basal diet treated rats. However, vitamin E deficiency alone resulted in reduced DOPA and dopamine in the striatum. The vitamin E deficient diets resulted in markedly lowered vitamin E levels in the striatum and substantia nigra. All of these effects were more profound in rats that had been maintained on a vitamin E deficient diet for 7 weeks than those that were so treated for 5 weeks. These results suggest that alterations in dopamine metabolism and endogenous antioxidant systems may interact. Neuroleptics such as haloperidol that acutely accelerate dopamine synthesis and metabolism may cause peroxidative stress as indicated by depletions of vitamin E. Such depletions are capable of reducing dopamine levels and synthesis. The possibility that this and the effect of chronic haloperidol are mediated by peroxidative damage to dopamine neurons must be considered.
VonVoigtlander
P F
PF
Upjohn Company, Kalamazoo, Michigan 49001.
Burian
M A
MA
Althaus
J S
JS
Williams
L R
LR
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000378:metabolism*
D015306:Biogenic Monoamines; D014810:Vitamin E; D012701:Serotonin; D006220:Haloperidol; D004298:Dopamine