Recent studies have indicated that the glutamatergic system is involved in the motivational aspects during the initiation of drug self-administration. Ascorbic acid (AA), an antioxidant vitamin, is released from glutamatergic neurons, and it modulates the synaptic action of dopamine and glutamate. In this study the AA effects on the self-administration of morphine and on the morphine withdrawal syndrome have been investigated. Wistar rats were allowed to self-administer morphine (1 mg/infusion) during 10 consecutive days for 2 h/session. The number of lever pressings was recorded. An intrapritoneal AA injection (500 mg/kg, i.p.), 30 min before morphine self-administration produced a significant decrease in the initiation of morphine self administration during all sessions. After the last test session morphine withdrawal symptom signs (MWS) were recorded after naloxone precipitation. Most of MWS (but not all) were decreased by AA application. In conclusion, AA may change the motivational processes underlying the morphine self-administration.