Antagonistic Activity of Ascorbic Acid (Vitamin C) on Dopaminergic Modulation: Apomorphine-Induced Stereotypic Behavior in Mice

Abstract

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 D₁ 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.

Ascorbic acid inhibits development of tolerance and dependence to opiates in mice: Possible glutamatergic or dopaminergic modulation

“…The prevention of development of tolerance and dependence to opiates in our study appears to be due to different components of action of AA. The inability of low dose of ascorbic acid (400 mg/kg) given chronically to alter tolerance or dependence is consistent with observation that, ascorbic acid at low doses, has potentiating action on dopaminergic and glutamatergic system918. Ascorbic acid at high doses (800-1600 mg/kg), however, has profound inhibitory role over NMDA receptor function and a haloperidol-like antidopaminergic activity719.…”

“…Ascorbic acid inhibited the binding of both dopamine agonists and antagonists in dose dependent manner23–25. Furthermore, ascorbic acid also potentiated antidopaminergic activity of haloperidol919. Similarly, ascorbic acid significantly potentiated the activity of MK 801 that has no effect either on development of tolerance or dependence to opioids at low dose (0.01 mg/kg).…”

“…Also, a growing body of research indicates that ascorbic acid is capable of modulating the effects of dopamine in the mammalian forebrain. Ascorbic acid enhanced the effect of catalepsy produced by dopaminergic antagonists as well as various nitric oxide synthase inhibitors89. Also ascorbic acid blocked the amphetamine-induced turning behaviours in rats with unilateral nigrostriatal lesion produced by 6-hydroxydopamine10.…”

“…These findings coupled with inhibition of dopamineric agonists and antagonists in radioligand binding studies suggested antidopaminergic-like action of ascorbic acid. Recently, we have shown that ascorbic acid potentates the antipsychotic activity of both typical and atypical antipsychotics thus possessing antidopaminergic effect9. Thus, it was hypothesized that ascorbic acid has protective effect in the development of tolerance and dependence by modifying the dopaminergic or glutamatergic neurotransmission.…”

Effects of co-administration of dopamine and vitamin C on ischaemia-reperfusion injury after experimental testicular torsion-detorsion in rats

“…However, in a previous work, the high density of receptors in rat testicular interstitial cells was reported, which suggests a role for dopamine in the control of vasodilation (Poyet & Labrie, 1986). Weak effect of combined administration of dopamine and vitamin C compared with the vitamin C alone may be explained when we know antagonistic activity of vitamin C on dopaminergic system (Deshpande et al. , 2006).…”