title: Combined treatment of ascorbic acid or alpha-tocopherol with dopamine receptor antagonist or nitric oxide synthase inhibitor potentiates cataleptic effect in mice.
abstract: BACKGROUND
  Drugs like haloperidol (Hal) that decrease dopamine (DA) neurotransmission in the striatum induce catalepsy in rodents and Parkinson disease-like symptoms in humans. Nitric oxide synthase (NOS) inhibitors interfere with motor activity, disrupting rodent exploratory behavior and inducing catalepsy. Catalepsy induced by NOS inhibitors probably involves striatal DA-mediated neurotransmission. Antioxidants such as ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have also been shown to interfere with movement modulation and the DA system.
  
  
  OBJECTIVE
  The objective of the study is to investigate if the antioxidants vitamins C and E would influence the catalepsy produced by Hal and NOS inhibitors.
  
  
  METHODS
  The effects of the following treatments on catalepsy were examined using the hanging-bar test on male Swiss mice (25-30 g): (1) vitamin C (30-1,000 mg/kg)xHal (1 mg/kg); (2) vitamin C (90-1,000 mg/kg)xN (G)-nitro-L: -arginine (LNOARG, 10 and 40 mg/kg); (3) vitamin C (300 mg/kg)xN (G)-nitro-L: -arginine methylester (LNAME, 20-80 mg/kg); (4) vitamin C (300 mg/kg) x 7-nitroindazole (7NI, 3-50 mg/kg); (5) vitamin C (90 mg/kg i.p.) x LNOARG [40 mg/kg twice a day during 4 days (subchronic treatment)]; (7) vitamin E (3-100 mg/kg) x Hal (1 mg/kg); and (6) vitamin E (3-100 mg/kg) x LNOARG (40 mg/kg).
  
  
  RESULTS
  Vitamin C enhanced the catalepsy produced by NOS inhibitors and Hal. Treatment with vitamin C did not affect tolerance to LNOARG cataleptic effect induced by subchronic treatment. Vitamin E potentiated the catalepsy induced by LNOARG at all doses tested; in contrast, catalepsy induced by Hal was enhanced only by the dose of 100 mg/kg.
  
  
  CONCLUSIONS
  Results support an involvement of dopaminergic and nitrergic systems in motor behavior control and provide compelling evidence that combined administration of the antioxidants vitamins C and E with either Hal or NOS inhibitors exacerbates extrapyramidal effects. Further studies are needed to assess possible clinical implications of these findings.
authors.affiliation: Department of Neurology, Psychiatry and Medical Psychology, School of Medicine, Campus USP, Av Bandeirantes 13400, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Lazzarini
authors.forename: C
authors.initials: C
authors.lastname: Salum
authors.forename: E A
authors.initials: EA
authors.lastname: Del Bel
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D013997:Time Factors; D014815:Vitamins / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D014815:Vitamins; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D024502:alpha-Tocopherol; D006220:Haloperidol; D001205:Ascorbic Acid; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester