Studies On The Interaction Of Addictive Drugs, Ascorbic Acid And Hippocampal Glutamatergic System

Abuse of addictive drugs has become more and more serious issue in the world. Previous studies have suggested that glutamatergic NMDA receptor is mainly involved in the ethanol-induced striatal AA release. The change of NR1, the major NMDA receptor subunit found in most or all NMDA receptor complexes, reflects the change of NMDA receptor in certain extent. The present studies by using immunohistochemical method detected the expression of NR1 in brain after ascorbic acid (AA) administration. The results showed that acute AA (100 mg/kg, i.p.) could increase the expression of NR1 in the striatum, nucleus accumbens (NAc) and hippocampus of the rat.The mechanism of ethanol-, morphine-, methamphetamine- (MAP), and nicotine-induced AA release in striatum and NAc is not well understood. Our previous studies have shown that the glutamatergic system is involved in the addictive drug-induced AA release in NAc and striatum. Furthermore, frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not in the NAc, suggesting other regions in the brain might be involved in accumbal AA release. It is reported that there exists a glutamatergic link between hippocampus and nucleus accumbens. In the present study, the roles of the hippocampus in drug-induced AA release in the striatum and NAc were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). Ethanol (3.0 g/kg, i.p.), methamphetamine (3.0 mg/kg, i.p.), and nicotine (1.5 mg/kg, i.p.) significantly stimulated AA release in the striatum and NAc, respectively. Morphine (20 mg/kg, i.p.) significantly stimulated AA release in the striatum, but not in the NAc. After hippocampus lesion by kainic acid, AA release induced by ethanol, methamphetamine, and nicotine could be eliminated in NAc, but not in the striatum. These results suggest that the hippocampus might play a crucial role in addictive drug-induced AA release in the NAc, which also imply that different pathways might be involved in drug-induced AA release in the striatum and the NAc of the rats.