Anticonvulsant Effect of Minocycline on Pentylenetetrazole-Induced Seizure in Mice: Involvement of 5-HT3 Receptor.

Minocycline, widely used as an antibiotic, has recently been found to have an anti-inflammatory, neuroprotective and anticonvulsant effects. This study was aimed to investigate the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures considering the possible involvement of 5-HT3 receptor in this effect. For this purpose, seizures were induced by intravenous PTZ infusion. All drugs were administrated by intraperitoneal (i.p.) route before PTZ injection. Also, 1-(m-chlorophenyl)-biguanide (mCPBG, a 5-HT3 receptor agonist) and Tropisetron (a 5-HT3 receptor antagonist) were used 45 minutes before minocycline treatment. Our results demonstrate that acute minocycline treatment (80 and 120 mg/kg) increased the seizure threshold. In addition, the 5-HT3 antagonist, tropisetron, at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of minocycline (40 mg/kg), while mCPBG (0.2 mg/kg) blunted the anticonvulsant effect of minocycline (80 mg/kg). In conclusion, our findings revealed that the anticonvulsant effect of minocycline is mediated, at least in part, by inhibition of 5-HT3 receptor.

The effectiveness of continuous and interval exercise preconditioning against chronic unpredictable stress: Involvement of hippocampal PGC-1α/FNDC5/BDNF pathway.

Various exercise-training types are known to prevent depression, but mechanisms underlying their beneficial effects remain unknown. In the present study, the preconditioning effect of continuous and interval exercise on stress-induced depression was evaluated. Adult male Wistar rats in the exercise groups were made to run on a motorized treadmill, five sessions per week for six weeks. After that, to induce the depression model, the rats were exposed to chronic unpredictable stress for three weeks. Behavioral tests were assessed by open field, elevated plus maze, and forced swim tests. Hippocampal PGC-1α, FNDC5, and BDNF protein expression by Western blot and serum corticosterone by ELISA were detected. In the present results, after continuous and interval exercise periods, locomotor activity, the number of entries and time spent in the open arms were increased, and immobility time was significantly reduced. PGC-1α, FNDC5, and BDNF protein levels had a significant increase, and serum corticosterone did not change. Also, interval exercise training increased PGC-1α and FNDC5 more than continuous. Chronic unpredictable stress reduced the positive changes caused by exercise training, although, except FNDC5, exercise preconditioned groups experienced less significant adverse changes in most variables. These findings showed that both continuous and interval exercise preconditioning with increasing hippocampal PGC-1α, FNDC5, and BDNF proteins and improve the anxiety- and depression-like behaviors have a protective effect against chronic unpredictable stress.