Glutamate Concentration In Nucleus Accumbens Research Articles

No effect of riluzole and memantine on learning deficit following quinpirole sensitization - An animal model of obsessive-compulsive disorder

RationaleChronic quinpirole (QNP) sensitization is an established animal model relevant to obsessive-compulsive disorder (OCD) that has been previously shown to induce several OCD-like behavioral patterns, such as compulsive-like checking and increased locomotion. ObjectivesIn current study we explored the effect of antiglutamatergic drugs, memantine and riluzole, on cognitive and behavioral performance of QNP sensitized rats. MethodsDuring habituation phase, the rats (N = 56) were injected with QNP (0.25 mg/kg) or saline solution (every other day up to 10 injections) and placed into rotating arena without foot shocks for 50-min exploration. Active place avoidance task in rotating arena with unmarked to-be-avoided shock sector was used during acquisition phase. Rats were injected with memantine (1 mg/kg or 5 mg/kg), riluzole (1 mg/kg or 5 mg/kg) or saline solution 30 min before the trial and with QNP (0.25 mg/kg) or saline right before they were placed inside the rotating arena with 60° unmarked shock sector. Locomotion and number of entrances into the shock sector were recorded. ResultsQNP sensitization led to a robust deficit in place learning. However, neither memantine nor riluzole did reverse or alleviate the deficit induced by QNP. Contrarily, memantine significantly aggravated QNP induced deficit. ConclusionsThe exacerbation of cognitive deficit following antiglutamatergic agents could be mediated by decreased glutamate concentration in nucleus accumbens and decreased hippocampal activation in the QNP sensitization model.

Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using 1H MRS.

IntroductionThe diagnosis of psychoactive substance use disorders has been based primarily on descriptive, symptomatic checklist criteria. In opioid addiction, there are no objective biological indicators specific enough to guide diagnosis, monitor disease status, and evaluate efficacy of therapeutic interventions. Proton magnetic resonance spectroscopy (1H MRS) of the brain has potential to identify and quantify biomarkers for the diagnosis of opioid dependence. The purpose of this study was to detect the absolute glutamate concentration in the nucleus accumbens (NAc) of patients with prescription opioid dependence using 1H MRS, and to analyze its clinical associations.MethodsTwenty patients with clinically diagnosed definitive prescription opioid dependent (mean age = 26.5 ± 4.3 years) and 20 matched healthy controls (mean age = 26.1 ± 3.8 years) participated in this study. Patients were evaluated with the Barratt Impulsiveness Scale (BIS‐11), the Self‐Rating Anxiety Scale (SAS), and the opiate Addiction Severity Inventory (ASI). We used point‐resolved spectroscopy to quantify the absolute concentrations of metabolites (glutamate, choline, N‐acetylaspartate, glutamine, creatine) within the NAc. The difference between metabolite levels of groups and Pearson's correlation between glutamate levels and psychometric scores in patients were analyzed statistically.ResultsGlutamate concentrations in the NAc were significantly higher in prescription opiate addicts than in controls (t = 3.84, p = .001). None of the other metabolites differed significantly between the two groups (all ps > .05). The glutamate concentrations correlated positively with BIS‐11 scores in prescription opiate addicts (r = .671, p = .001), but not with SAS score and ASI index.ConclusionsGlutamate levels in the NAc measured quantitatively with in vivo 1H MRS could be used as a biomarker to evaluate disease condition in opioid‐dependent patients.

Ceftriaxone attenuates ethanol drinking and restores extracellular glutamate concentration through normalization of GLT-1 in nucleus accumbens of male alcohol-preferring rats

Alteration of glutamatergic-neurotransmission is a hallmark of alcohol dependence. We have previously reported that chronic ethanol-drinking downregulated glutamate transporter 1 (GLT-1) in nucleus accumbens (NAc) in male P rats in a manner that was reversed by ceftriaxone treatment. However, the effect of ceftriaxone on extracellular glutamate concentrations in NAc after chronic ethanol-drinking has not yet been studied. In the present study, male P rats were treated with ceftriaxone (100 mg/kg/day, i.p.) for five consecutive days following five-weeks of free choice ethanol (15% and 30%) drinking. In vivo microdialysis was performed to measure the extracellular glutamate concentrations in NAc and the effect of blockade of GLT-1 with dihydrokainic acid (DHK) on extracellular glutamate in NAc of ceftriaxone-treated rats was determined. Ceftriaxone treatment attenuated ethanol intake as well as ethanol preference. Extracellular glutamate was significantly higher in NAc after five-weeks of ethanol drinking in saline-treated compared to water control rats. Ceftriaxone treatment blocked the increase extracellular glutamate produced by ethanol intake. Blockade of GLT-1 by DHK reversed the effects of ceftriaxone on glutamate and implicated the role of GLT-1 in the normalization of extracellular glutamate by ceftriaxone. In addition, GLT-1 protein was decreased in ethanol exposed animals and ceftriaxone treatment reversed this deficit. Ceftriaxone treatment also increased glutamine synthetase activity in NAc but not in PFC as compared to ethanol drinking saline-treated rats. Our present study demonstrates that ceftriaxone treatment prevents ethanol drinking in part through normalization of extracellular glutamate concentrations in NAc of male P rats via GLT-1.