Ali Moghimi

The effect of minocycline on seizures induced by amygdala kindling in rats

PURPOSEnMinocycline is known as a chemical with neuroprotective, anti-inflammatory, and antimicrobial properties. In this study, the effects of minocycline on seizures induced by amygdala kindling in rats were studied.nnnMETHODSnKindled Wistar rats were injected intraperitoneally with saline and, on the following day, with minocycline (50, 25, and 12.5mg/kg for the three groups (1-3), respectively). The animals in groups 1-3 had similar protocols. Groups 4 and 5 were given for the rotarod test and received 25 or 50mg/kg minocycline, respectively, without any kindling stimulation. The animals in groups 6 and 7 (seven each) received 25mg/kg minocycline or saline, respectively. All the injections were carried out 1h before kindling stimulation. Seizure parameters, including after discharge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and seizure duration (SD), were recorded and compared with those of the saline groups.nnnRESULTSnMinocycline (50mg/kg) significantly reduced ADD, 1/S4L, S5D, and SD (P<0.001, P<0.05, P<0.001, and P<0.001, respectively) in group 1. While the administration of 25mg/kg of minocycline decreased the ADD and S5D (P<0.05), in group 2. The injection of 12.5mg/kg resulted in decreased S5D (P<0.001) in group 3. The daily injection of minocycline (25mg/kg) significantly decreased ADD, S5D, and SD (P<0.001) in group 6.nnnCONCLUSIONnThe obtained results revealed that minocycline has anticonvulsant effect on seizures induced by amygdala kindling. Thus, it may be useful for epilepsy treatment.

Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

Citicoline (cytidine-5-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (P<0.05). Citicoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (P<0.05). Additionally, citicoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (P<0.05). The pentobarbital induced sleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect.

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol kindled rats

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin‐A and orexin‐B are brain neuropeptides originating from postero‐lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB‐334867) on seizure‐ and anxiety‐related behaviors of pentylenetetrazol (PTZ)‐kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two‐day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB‐334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure‐related behaviors were monitored for 30 min following PTZ administration. The anxiety‐like behaviors were also assessed using elevated plus‐maze in the first and last days of the study. The results revealed that ICV injection of SB‐334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ‐induced anxiety‐like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.