Beyond Seizure Suppression: Caffeic Acid Phenethyl Ester and 10-Hydroxy-2-Decenoic Acid Improve Anxiety-like and Cognitive Behaviors in PTZ-Challenged Zebrafish

Epilepsy is associated with recurrent seizures and behavioral and cognitive disturbances, highlighting the importance of assessing behavioral outcomes alongside seizure severity. Caffeic acid phenethyl ester (CAPE) has shown neuroprotective activity, whereas evidence for the neurobehavioral effects of 10-hydroxy-2-decenoic acid (10-HDA) remains limited. This study investigated their individual and combined dietary effects on seizure-like behavior and behavioral test performance in adult zebrafish (Danio rerio) challenged with pentylenetetrazol (PTZ). Fish received experimental diets for 8 weeks before exposure to 15 mM PTZ. A dietary valproic acid group was included as a comparator. Outcomes included behavioral seizure scores, the area under the seizure score–time curve (AUC), and performance in the novel tank diving and Y-maze tests. Compared with PTZ alone, CAPE, 10-HDA, and their combination reduced seizure scores and AUC values and increased upper-zone and novel-arm exploration (p < 0.05). The combined group spent more time in the novel arm than either single-compound group (p < 0.05), although its advantages varied across endpoints and pharmacological synergy was not established. Overall, dietary CAPE and 10-HDA were associated with lower behavioral seizure scores and improved test performance following acute PTZ challenge. Further studies are needed to distinguish these responses from independent effects on baseline behavior and the influence of seizure severity and motor function.