Somogyi, G. | Search bioRxiv

bioRxiv2020

Absence-like epileptic spike-wave discharges in adult Lister Hooded rats and their pharmacological modulation

Efforts to advance translation through pre-clinical behavioural and pharmacological tests prompted attention to rat strain differences. Particularly the use of touchscreen technology for cognitive testing initiated the widespread use of Lister Hooded and Long Evans rats and they differed in pharmacological sensitivity to certain drugs. One possible reason for this rat strain difference could be that Long Evans rats produce high-amplitude spike-wave discharges (SWDs) in their cortical EEG recordings, while no information available about Lister Hooded rats in this regard. As a serendipitous observation, we noticed the presence of SWDs during the EEG recordings of Lister Hooded rats. In this study, therefore, we examined these spontaneous SWDs in two groups of Lister Hooded rats. The number and sum duration of the SWDs were similar to that was observed in other rat strains. We found SWDs during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, their duration was the longest during wakefulness, but their number and sum duration were also high during REM. The GABA-B receptor agonist baclofen exacerbated, while the GABA-B antagonist SCH50911 reduced the occurrence of the recorded SWDs. Typical anti-seizure medications, valproate and diazepam, decreased the number and sum duration of SWDs. Although the two rat strains typically used in touchscreen experiments are similar in term of SWDs, the occurrence and possible pharmacological modulation of SWDs are considerable during their use in behavioural experiments.

neuroscience↗

bioRxiv2020

Deciphering the scopolamine challenge rat model by preclinical functional MRI

During preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.

neuroscience↗