The effects of ascorbic acid injection in to locus ceruleus and ventral tegmental area and PGi on morphine withdrawal signs in rats

Background: Recent studies indicate that the glutamatergic and dopaminergic systems are involved in morphine withdrawal syndrome. Ascorbic acid (ascorbate) is an antioxidant vitamin released from glutamatergic neurons and modulates the synaptic action of dopamine and glutamate in the locus ceruleus, ventral tegmental area and PGi as well as behavior. Objective: To determine the effects of ascorbic acid injection into locus ceruleus, ventral tegmental area and PGi on morphine withdrawal signs in rats (MWS). Methods: This was an experimental study in which a total of 80 male rats (250-300gr) divided into two were tested. The first group marked as control received 3% sucrose in tap water (n=10) and the second group (dependent group) received morphine and 3% sucrose in tap water (0.1, 0.2, 0.3, 0.4mg/ml each for 48h, and 0.4mg/ml for the remaining days up to day 21). The latter was further divided into 7 subgroups as follows: (1) morphine group [2, 3, and 4] sham operated groups which were surgically implanted with cannula at the locus ceruleus (LC), ventral tegmental area (VTA), and PGi [5, 6, 7] morphine-ascorbic acid groups injected with AA (8 µg/µl) into LC, VTA, and PGi at day 21 and 5 min before naloxone administration. At the end of the training day, all groups received naloxone (2mg/kg I.P) and MWS was studied for 30 minute. Findings: Our results showed that the injection of ascorbate into LC and PGi caused a higher decrease in morphine withdrawal syndrome signs compared to VTA. Conclusion: Glutamatergic system is more effective than dopaminergic system in attenuation of MWS by acute injection of ascorbate.