The role of spinal serotonergic system in morphine withdrawal syndrome in the rat



Previous pharmacological studies have implicated serotonergic brain systems in opiate withdrawal syndrome. Increased brain 5-HT release is associated with the development of physical dependence to morphine. Specific serotonin reuptake inhibitors, such as fluvoxamine and sertraline reduce the severity of naloxone precipitated opioid withdrawal syndrome. Other studies have shown that 5-HT system is not directly responsible for the development of the withdrawal syndrome in morphine-dependent rats. In view of these evidences, the exact role of the spinal 5-HT systems remains unclear. This study aimed to investigate the effect of spinal serotonin on the morphine withdrawal syndrome. A total of 42 male Wistar rats weighing 220-250 g were used. Physical dependence was induced by i.p. injection of morphine at a schedule of 5 mg/kg for 3 days, 7.5 mg/kg for 2 days and 10 mg/kg for 2 days. Naloxone (1 mg/kg, i.p.) precipitated withdrawal behaviors such as jumping, tremor, abdominal writhing and wet dog shake were assessed 15 min after naloxone injection for 30 min. Results obtained from this study showed that 5-HT significantly attenuates (P<0.01) all of the above behaviors, both in chronic (200 µg/rat, i.t. for 7 days) and acute (200 µg/rat, i.t.) administration. Lesion of serotoninergic neurons by 5,7-DHT (100 µg/rat, i.t.) had not significant effect on jumping and wet dog shake behaviors, but decreased (P<0.05) severity of abdominal writhing and tremor. The results may indicate that morphine withdrawal syndrome is mediated through functional alterations in spinal cord serotoninergic system.