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Objective: In this study, our aim was to reveal the possible anticonvulsant effects of oxytocin (OX) in high doses, as oxytocin has inhibitory effects in brain. In addition, these effects were correlated with thalamic EEG recordings. To create the convulsions, pentilentetrazol (PTZ) was used.
Materials-Methods: In this study sixty 8-12 weeks old Sprague-Dawley adult male rats, which were separated into 10 groups (n=6), were used. In the first through the fifth groups 10, 20, 40, 80, and 120 U/kg OX was injected intraperitoneally (i.p) in order. In the sixth group (control), saline was injected. Five minutes after of each injection of OX, 70 mg/kg i.p. PTZ was injected into the all rats and seizures were induced. We evaluated the seizure behaviors with the Racine Convulsion Scale and we determined the threshold seizure dose of PTZ, around 35 mg/kg, and the suppressive dose of OX, around 80 and 120 U/kg. The rats, which were placed in a Plexiglas cage, were evaluated according to the severity of convulsions from 0 to stage 5. The scale of convulsions was: (0):Normal,(1):Frozen,(2):Nodding,(3):Superficial clonic movements,(4): Bilateral clonus in front extremities (piano play)(5):generalized tonic clonic seizures and falling sideways. To show the anticonvulsant effects of oxytocin using the EEG, the seventh through the tenth groups were used. Under anesthesia a small hole was drilled. Then by taking the bregma as a reference using the stereotaxic method (coordinates AP:-3.6 mm, L:+2.8 mm, V:-5.0 mm)(Paxinos Rat Brain), an exterior insulated bipolar EEG electrode was placed in the left thalamic nucleus. In the seventh group thalamic EEG records were taken after only saline injection. The rats in the eighth and ninth groups were injected intraperitoneally (ip) with 80 and 120 U/kg OX , respectively. In the tenth group (control), just saline was injected. Five minutes after each OX injection, 35 mg/kg i.p. PTZ was injected into the all rats. EEG recordings were taken for 20 minutes. The signals were amplified by 10,000 times and filtered with a range of 1-60 Hz. System records were taken by a Biopac MP30 amplifier system and evaluated with the FFT (Fast Fourier Transform) and PSA (Power Spectral Analyses) methods. During this process Delta 1-4 Hz, Theta 4-8 Hz, alpha 8-12 Hz and beta 12-20 Hz waves in the EEG are accepted as the ratio of percentage in PSA methods. We affirmed the electrode location histologically following euthanisation.
Results: We observed that oxytocin has a powerful anticonvulsant effect, which appears at 40 U/Kg (Stage 3.14±0.69 ) and 80 U/kg (Stage 3.0±0.57) doses moderately and which shows the maximum effect at 120 U/kg (Stage 1.57±0.53) doses (p<0.005). After injection of subconvulsive dose of PTZ (35mg/kg) and saline, the thalamic EEG delta frequency percentage was 54.6%±2.16 and after injection of only saline the thalamic delta frequency percentage was 80.5%±3.08. We observed significant (p<0.005) diminution in delta frequency and also augmentation in theta frequency. The augmentation of thalamic EEG frequency is linked to the GABA blocker effects of PTZ. After injection of a subconvulsive dose PTZ (35mg/kg) and saline, the thalamic EEG Delta frequency percentage was 54.6%±2.16 and in the rats given PTZ and 120 U/kg oxytocin the thalamic delta frequency percentage was 94%±1.41. In comparison there was a significant augmentation in delta frequency (p<0.005), and a diminution in theta frequency was observed. In PTZ and saline injected rats, the EEG formed spike-wave complexes. In the 120U/kg oxytocin and PTZ injected rats, the spike-wave complexes disappeared.
Conclusion: Our results indicate that Oxytocin has therapeutic potential similar to anticonvulsants in epilepsy.