Response Characteristics to Pentylenetetrazol Administration in Rats with the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

• Published in: Journal of evolutionary biochemistry and physiology Vol. 61; no. 4; pp. 1179 - 1188
• Main Authors: Subkhankulov, M. R., Zubareva, O. E.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.07.2025; Springer Nature B.V
• Subjects: Animal models; Animal Physiology; Biochemistry; Biomedical and Life Sciences; Convulsions & seizures; EEG; Electroconvulsive therapy; Epilepsy; Evolutionary Biology; Experimental Papers; Life Sciences; Lithium; Lithium chloride; Pilocarpine; Seizures; Sleep deprivation; Temporal lobe; temporal lobe epilepsy; epileptiform activity; pentylenetetrazol; lithium-pilocarpine model; maximal electroshock; EEG; provocative tests
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093025040180

Epilepsy is a severe neurological disorder, with approximately 30% of patients exhibiting therapy resistance. The lithium-pilocarpine model of temporal lobe epilepsy (TLE) in rats reproduces key features of the disease, but long-term monitoring of spontaneous seizures is time-consuming and labor-intensive, necessitating the search for additional biomarkers of epileptogenesis. In clinical practice, EEG—particularly the analysis of interictal epileptiform patterns—plays a crucial role in epilepsy diagnosis. Provocative tests (sleep deprivation, photic stimulation, etc.) enhance the detection of pathological patterns. In experimental settings, a similar effect can be achieved using low doses of convulsants, such as pentylenetetrazol (PTZ), though such methods are rarely employed. The aim of this study was to investigate the effect of low-dose PTZ on epileptiform activity in the lithium-pilocarpine TLE model in rats and compare this method with maximal electroshock (MES) testing. The TLE model was induced in male Wistar rats (experimental group: pilocarpine following LiCl pretreatment; control group: saline). Six months after the development of spontaneous recurrent seizures, EEG electrodes were implanted onto the skull surface. EEG recordings were conducted in two phases: baseline and following PTZ administration (40 mg/kg). Three weeks later, seizure susceptibility was assessed using MES. The results showed that baseline EEG recordings revealed no differences between the groups. However, after PTZ administration, a clear distinction was observed: Control rats exhibited regular bursts of high-amplitude sharp waves (4–8 Hz), whereas rats with the epilepsy model predominantly displayed interictal spikes and spike-wave complexes. In contrast, MES testing revealed no differences in the threshold currents for inducing hindlimb extension between control and experimental rats. Thus, the provocative test using low-dose PTZ is a highly sensitive method for detecting epileptiform activity in the TLE model, providing greater diagnostic value than MES testing. These findings support the potential of this approach for preclinical research.