Antagonistic activity of ascorbic acid (vitamin C) on dopaminergic modulation: apomorphine-induced stereotypic behavior in mice.
Among the various neurotransmitter systems implicated in the mechanism of action of ascorbic acid (vitamin C), the relationship between the dopaminergic system and ascorbic acid is not particularly clear. Ascorbic acid is speculated to have an antagonistic effect on dopaminergic modulation. With this background in mind, in the present study we have seen the effect of ascorbic acid per se and in combination with typical and atypical antipsychotic agents against apomorphine-induced stereotypic behavior in mice. Male Laka mice weighing 20-25 g were used in the present study. Apomorphine-induced stereotypic behavior was used as an animal model. Various dopaminergic modulators were used. Ascorbic acid dose-dependently inhibited stereotypic behavior produced by apomorphine in mice. It potentiated the antipsychotic activity of haloperidol (0.1 mg/kg i.p.), a typical antipsychotic agent. When administered along with atypical antipsychotics, clozapine (1-2 mg/kg i.p.), sulpiride (10-20 mg/kg i.p.) and risperidone (0.0025 mg/kg i.p.), ascorbic acid also potentiated their activity. Also when given along with SCH-23390, a selective D(1) antagonist, an additive effect was observed. Ascorbic acid also inhibited the supersensitization response of apomorphine on reserpinization (2 mg/kg i.p.). Interestingly, at a lower dose (100 mg/kg i.p.), ascorbic acid potentiated the dopaminergic activity of apomorphine (0.5 mg/kg) and BHT-920 (0.25 mg/kg i.p.). However, when given concomitantly with SKF-38393, it failed to alter the response of SKF-38393. The data substantiate the hypothesis that ascorbic acid potentiated the activity of typical as well as atypical antipsychotics and that the effect of ascorbic acid on the dopaminergic system is markedly dose dependent; a low dose (100 mg/kg i.p.) potentiated the dopaminergic action while higher doses (400-1,600 mg/kg i.p.) blocked it.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Chandrashekhar
C
Deshpande
Ashish
A
Dhir
S K
SK
Kulkarni
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001205:Ascorbic Acid / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D000975:Antioxidants; D014150:Antipsychotic Agents; D001381:Azepines; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004338:Drug Combinations; C024763:talipexole; D013469:Sulpiride; D012110:Reserpine; D006220:Haloperidol; D001058:Apomorphine; D001205:Ascorbic Acid