Sodium valproate and gabapentin reduce the seizure-like behavior induced by pentylenetetrazol and mechanical stress in Drosophila melanogaster: sex influence on behavioral responses.

Epilepsy is a multifactorial neurological condition characterized by abnormal, recurrent neuronal discharges. The search for new anticonvulsant treatments requires experimental models that replicate the pharmacological responses of drugs commonly used for this condition. This study aimed to evaluate the effect of pentylenetetrazol (PTZ), a pro-convulsant agent, combined with thermal or mechanical stress, on seizure-like behavior in female and male D. melanogaster. Moreover, to determine the response to anticonvulsant drugs. Initially, the locomotor activity of the flies was evaluated after exposure to PTZ (0.1-60 mM) to rule out potential baseline locomotor deficits that could interfere with the results. Next, the flies were exposed to PTZ for 24 h and subjected to thermal or mechanical stress to induce seizure-like behavior. From the results, exposure to PTZ (1 mM) associated with vortex-induced mechanical stimulation was selected for inducing seizure-like behaviors in both male and female flies. Subsequently, the groups were treated with anticonvulsant drugs, sodium valproate (0.1, 1.0, 10 mM) or gabapentin (0.5, 1.0, 2.5 mM). Both drugs attenuated the seizure-like behaviors induced by PTZ and mechanical stress, showing higher effects in males. In conclusion, PTZ, associated with mechanical stress, reproduces a phenotype resembling seizure-like behavior in male and female D. melanogaster. Furthermore, the model was responsive to sodium valproate and gabapentin, especially in male flies, supporting its translational potential for identifying new drugs and reinforcing the importance of including sex as an experimental variable.