Acute agomelatine administration does not attenuate deficits in vocalizations, inflammation, or excitation in kainic acid treated pups.
Access changed 8/24/22
Seizures during early-development result in an increase in proinflammatory cytokine production and impact communication behavior in murine models. Our study investigated the efficacy of the anti-inflammatory pharmaceutical agomelatine on neuroinflammatory processes and ultrasonic vocalizations (USVs) in mice. On postnatal day (PD) 10 male and female C57 BL6/J mice were administered kainic acid (KA) to induce status epilepticus (SE). The mice then received either agomelatine, DMSO (vehicle), or saline either 1-hour post SE or 24 hours post SE. The early life communication behavior ultrasonic vocalizations was evaluated on PD 11 and 12 and western blotting was conducted on PD 15. While KA administration lead to an increase in vocalizations overall on PD 11 at the 1-hour timepoint, agomelatine was unable to attenuate this deficit. No main effects of seizures were observed on PD 12 1-hour post treatment or on PD 11 or PD 12 in the 24-hour post treatment groups. When the quantity of USVs emitted per each call type was assessed, agomelatine was similarly unable to attenuate the increased quantity of frequency steps, upward, downward, chevron, and composite call types observed throughout the 1-hour and 24-hour treatment groups. Similarly, the KA induced alterations in the average duration, peak frequency, fundamental frequency, and amplitude of the call types were also not altered by agomelatine administration. When markers of excitation and inflammation were assessed via western blotting, KA was found to increase GFAP, Iba1, and GluR1 relative to controls, with no significant difference present in the expression of mGluR1/5. Agomelatine did not significantly alter this upregulation. Overall, our study suggests that despite its high theoretical promise, agomelatine displays minimal efficacy to treat aberrant vocalizations, excitation, and neuroinflammation in neonates administered KA.