Banca de QUALIFICAÇÃO: ANTONIO JHONES LIMA DA ROCHA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANTONIO JHONES LIMA DA ROCHA
DATE: 17/12/2025
TIME: 09:00
LOCAL: INSTITUTO DO CEREBRO - Sala de Reuniões
TITLE:

Refined Behavioral Quantification of PTZ-Induced Seizures and the Modulatory Effects of Phytocannabinoids

KEY WORDS:

Epilepsy; Limbic Seizures; Phytocannabinoids; Pentylenetetrazol;

...

PAGES: 70
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

Detailed behavioral characterization of seizures is essential for improving the precision and reproducibility of preclinical epilepsy research. Although various experimental models exist, the Racine scale remains the most widely used metric for quantifying seizure severity. Originally developed for electrical kindling, the scale primarily captures the progressive recruitment of limbic motor behaviors. However, when applied to chemoconvulsant models such as pentylenetetrazole (PTZ), the Racine scale fails to encompass the full behavioral spectrum induced by this GABAergic antagonist. Following a high dose of PTZ, mice display a sequence of ictal events such as spasms, myoclonias, and limbic seizures. Because only limbic seizures are represented in the Racine scale, important early and later ictal behaviors remain overlooked. To address this limitation, our project employed a refined approach combining detailed video tagging and automated tracking to identify and quantify spasms and myoclonias as behavioral events distinct from limbic seizures. This method offered a more comprehensive view of PTZ-induced acute seizures and was also applied to PTZ-kindling paradigms, in which repeated low doses progressively altered the severity and temporal structure of ictal behaviors. By distinguishing early ictal-related expressions, our approach enhances sensitivity to treatment-induced modulation and improves overall behavioral resolution. Using this refined methodology, we investigated the effects of three phytocannabinoids—cannabidiol (CBD), cannabinol (CBN), and cannabigerol (CBG)—on acute seizure expression. Animals received a single intraperitoneal injection of CBD, CBN, or CBG (3, 30, or 300 mg/kg) or vehicle (corn or MCT oil) and were monitored for one hour before PTZ administration (60 mg/kg, s.c.). Across phytocannabinoid treatments, no significant differences were observed in spasm latency, spasm number, or inter-spasm intervals. A negative correlation emerged between the number of spasms and their inter-event interval, reflecting greater event clustering in animals with higher spasm counts. Myoclonias similarly showed no major treatment-related differences, except for an increased number of events in the CBN-300 group. None of the phytocannabinoids altered limbic seizure incidence, latency, or duration, while diazepam fully prevented limbic seizures, as expected. Temporal analyses revealed more nuanced treatment effects. Cumulative event curves and episode-distribution analyses showed that certain CBD and CBG doses collapsed the typical bimodal distribution of spasms and myoclonias into a single consolidated peak, shifting event expression toward specific post-PTZ windows. CBN, in contrast, tended to preserve or broaden the bimodal profile depending on the dose. Additionally, phytocannabinoid treatment produced dose-dependent locomotor alterations, such as reduced center exploration, speed, and total distance traveled. Taken together, these findings highlight the limitations of traditional seizure scoring methods and underscore the value of refined behavioral quantification in PTZ models. Although the tested phytocannabinoids did not prevent or reduce the occurrence of ictal events, they modulated the temporal organization of ictal behaviors and influenced locomotor activity. Future studies should examine corresponding electrophysiological signatures and explore intermediate doses and time points to further elucidate phytocannabinoid actions in seizure modulation.

COMMITTEE MEMBERS:
Interno - 1721223 - ADRIANO BRETANHA LOPES TORT
Presidente - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 1842426 - SERGIO TULIO NEUENSCHWANDER MACIEL