The effect of vitamin C on morphine self-administration in rats

Abstract

Background:Recent studies have shown that addiction may be caused by abnormality of neurotransmission in the brain. Two neurotransmitters that involve into morphine addiction are dopamine and glutamate. The glutamatergic and dopaminergic systems are also involved in morphine tolerance and morphine withdrawal syndrome signs. Ascorbic acid (AA), as the antioxidant releases from the glutamatergic neurons, modulates the action of the dopamine and glutamate systems. In this study, the effect of AA on morphine self-administration and morphine withdrawal symptoms has been investigated.Materials and Methods:Male Wistar rats (250 - 300g) were anesthetized with ketamine (11%) and xailazine (15%). The cannula was inserted into the right jugular vein, and it was fixed subcutaneously on the skull. After surgery the animals were placed in individual home cages, and they were allowed to recover from the operation for five days, before the test. The animals were subjected to self-administration morphine for12 consecutive days, two-hour/sessions. The number of infusions and number of active and passive lever pressings were recorded.Results:An intra peritoneal injection of Ascorbic acid (AA) (400 mg/kg, i.p.), 30 minutes before morphine self-administration, produced a significant decrease in 12 days self-administration of morphine and withdrawal syndrome signs (P < 0.05). The morphine withdrawal signs (MWS) were recorded after naloxone precipitation, which decreased significantly with the injection of AA (400,700mg/kg), (<0.05). The number of self-infusions and the number of active lever pressings had significantly decreased after AA injection (P < 0.05).Conclusion:The chronic administration of AA may prevent the development of tolerance and physical dependence on morphine self-administration via the glutamatergic system.

Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System

“…Repeated administration of opioids including morphine is known to damage cells and tissues through the generation of ROS and suppression of antioxidant genes resulting in opioid-induced disorders such as addiction and MAT [ 4 , 52 , 53 ]. The supplementation of antioxidants is shown to improve the disturbance of redox homeostasis induced by morphine [ 7 , 8 , 9 , 10 ]. To verify this phenomenon THP cells were treated either with MPDA, morphine, and MPDA@Mor with DMEM as a positive control.…”

“…Concurrently MPDA@Mor chronic administration significantly reduced TNF-α and NFkb protein levels in DRG compared with the morphine group ( Figure 7 c,d, red bars). Thus, we postulated that MPDA@Mor can alleviate MAT through the inhibitions of glial-derived pro-inflammatory cytokine activation which could be attributed to the antioxidant properties of MPDA, as the administration of exogenous antioxidants has been shown to attenuate MAT through the suppression of pro-inflammatory cytokine levels by several reports [ 7 , 8 , 9 , 10 ].…”

“…Many studies have demonstrated that suppression of ROS by antioxidants or deletion of ROS causing genes such as nitric oxide synthase (NOS) could attenuate MAT in various animal models [ 4 , 7 , 8 , 9 , 10 , 11 ]. Though natural antioxidants have phenomenal ROS scavenging ability, clinical trials have shown limited success in preventing ROS related diseases with toxicity at high doses [ 12 , 13 ].…”

The role of vitamin C in the treatment of pain: new insights

“…Co-administration of 1 g/kg vitamin C with morphine prevented the development of morphine tolerance and physical dependence in mice [ 101 ]. Intraperitoneal administration of 400 mg/kg vitamin C significantly decreased self-administration of morphine and withdrawal syndrome signs in rats [ 102 ]. Vitamin C itself was shown to have antinociceptive effects in mice (ED50 of 206 mg/kg).…”

Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk

“…Few studies have been carried out in humans, but some small cohorts have shown reduced circulating vitamin C levels in chronic opioid users [ 12 , 13 ]. Treatment with vitamin C has been shown to decrease opioid withdrawal symptoms in guinea pigs [ 14 ], rats [ 15 ], and humans [ 16 , 17 ]. AA has been described as a solubilizing agent for street heroin base, although the amount of AA required is far below the amounts used in laboratory and clinical research settings [ 18 , 19 ].…”