Opiate abuse is associated with long-lasting neural adaptative changes in the brain. Increasing evidence demonstrates that opiates significantly alter the function of the glutamatergic system, while how the system is regulated still remains elusive. In the present study, we studied the effect of morphine on extracellular glutamate concentration in the hippocampus, a nucleus rich of the glutamatergic neurons. The results showed that glutamate concentration in the extracellular fluid of the hippocampus was decreased following either acute or chronic treatment of morphine. However, naloxone-induced withdrawal increased glutamate concentration significantly. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine treatment.

Previous studies have shown that acute systemic administration of ethanol-induced striatal ascorbic acid (AA) release in mice and rats. In the present study, in vivo brain microdialysis coupled with high performance liquid chromatography (HPLC) with electrochemical detection (ECD) was used to comparatively evaluate the effects of clozapine on ethanol-induced AA release in mouse and rat striatum. The results showed that clozapine, at the dose of 15mg/kg i.p., had no effect on basal AA or ethanol-induced AA release in rat striatum. The potentiating effect of clozapine on ethanol-induced striatal AA release was still observed in rats, at the higher dose of 30mg/kg. In contrast, clozapine significantly inhibited ethanol-induced AA release in mouse striatum, at the dose of 15 and 30mg/kg, without affecting basal AA release. The present study suggested that clozapine differentially regulated ethanol-induced AA release in the mouse and rat striatum.

Social isolation can induce psychological behavior changes. It is interesting to know whether there is sex difference in responding to social isolation or not. The present study compared the behavior difference between male and female mice isolated for 1-4 months. The results showed that the isolated male mice had higher accounts of locomotor activity than the isolated female and group-housed ones. Both isolated male and female mice spent shorter time in the dark box than the group-housed mice in the light/dark test, and isolated male mice spent less time in the closed arms than isolated female and group-housed mice when isolated for 2, 3 and 4 months in the elevated plus-maze test. These results suggest that isolation induce an anxiolytic-like effect. The immobile time in the forced swimming test was shortened in male mice isolated for 1 and 2 months. Both isolated male and female mice showed shorter time in pentobarbital-induced loss of righting reflex and less body weight gain. These results demonstrated that there was a sex difference in psychological behavior changes in mice undergoing social isolation and the male mice were more easily affected by isolation.

In the present study, in vivo brain microdialysis coupled with high performance liquid chromatography (HPLC) and electrochemical detection were used to evaluate the effects of either L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS), Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), a non-selective NOS inhibitor, or sodium nitroprusside (SNP), a donor of NO, on the ethanol-induced release of ascorbic acid (AA) in the striatum of freely moving mice. Drugs were administered intrastriatally via the microdialysis probe and ethanol (2-4g/kg) was administered intraperitoneally. The results showed that L-arginine (1-10mg/ml) had no effect on either the basal AA contents in striatal extracellular fluid or the ethanol-induced release of AA. L-NAME (10−4 to 10−3mg/ml) and SNP (10−4 to 10−3mg/ml) both reduced the basal AA concentrations in striatal extracellular fluid. L-NAME significantly inhibited ethanol-induced release of AA, while SNP only had a transient inhibitory effect on the ethanol-induced release of AA. SNP significantly increased dehydroascorbic acid (DHAA) contents and DHAA/AA ratio but had no effect on the total AA contents (AA and DHAA contents) in striatal extracellular fluid, while L-NAME had no effect on DHAA contents but decreased the total AA contents in striatal extracellular fluid. Only high concentration L-NAME induced a transient increase in DHAA/AA ratio. Our results suggest that nitric oxide (NO) might not directly be involved in the mechanism of ethanol-induced release of AA in mouse striatum.

In the present study, pseudoginsenoside-F11 (PF11), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10mg/kg four times at 2-h intervals, and PF11 was orally administered at the doses of 4 and 8mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF11 did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF11 significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF11 greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF11 significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3, 4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5- hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF11 could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF11 is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.