Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants

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N-Acetylcysteine (NAC) has been in clinical practice for several decades as a mucolytic agent and has been used also for the treatment of paracetamol intoxication, doxorubicin- induced cardiotoxicity, stable angina pectoris, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome bronchitis, chemotherapy-induced toxicity, HIV/AIDS, radio contrastinduced nephropathy, heavymetal toxicity and psychiatric disorders including schizophrenia, bipolar disorder and addiction. It has been recently shown that NAC modulates the glutamatergic system through the system xc (Cystine-Glutamate Antiporter): Antiporter cysteine/glutamate. Ceftriaxone (CTX), a β-lactam antibiotic, is also shown to led to an increase of excitatory amino-acid transporter 2 (EAAT2) expression and glutamate transport activity in the brain in animal studies. It has been demonstrated that CTX has neuroprotective effects in both in vitro and in vivo models based on its ability to inhibit neuronal cell death by preventing glutamate excitotoxicity. The aim of the present study was to investigate the neurobehavioural effects of acute administration of NAC and CTX alone and in combination in open field and elevated plus maze tests. For this aim, three different doses (50, 100 and 200 mg/kg, i.p.) of CTX and NAC alone in the first part and their combination in the second part of the experiments and two different doses of diazepam were evaluated in open field and elevated plus maze tests. 200 mg/kg of NAC revealed anxiolytic-like behaviours in both tests while CTX 200 mg/kg failed to produce. Further investigations need to be conducted to rule out the involvement of system xc- on anxiety related behaviours. Increased system xc may represent an effective therapeutic endpoint.

J. Exp. Clin. Med., 2014; 31:43-50


Anxiety; ceftriaxone sodium; N-acetylcysteine; rats

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