There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spikeand-wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant-based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ 9tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2 hr. Injected THC (1-10 mg/kg, i.p.) dose-dependently increased SWDs to over 200% of baseline. In contrast, CBD (30-100 mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high-THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low-THC/high-CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pretreatment with a CB1R antagonist (SR141716A) did not prevent the high-THC cannabis smoke from increasing SWDs, suggesting that the THC-mediated increase may not be CB1R-dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti-epileptic effect. Together these experiments provide initial evidence
The TUNL task is an automated touchscreen task used to evaluate the cognitive processes involved in working memory (WM) and spatial pattern separation in rodents. Both rats and mice can be used. To elicit working memory processes, the rodent must distinguish between a sample (familiar) light stimulus and a novel light stimulus after a delay. With a correct selection, the rodent will receive a food reward. A major benefit of TUNL compared to other similar tasks is the circumvention of spatial "mediating strategies" that the rodent may use to supplement or replace working memory processes to complete the task successfully. Each trial is 'unique', as the stimuli are pseudo-randomized between trials in an array of spatial locations. The TUNL task uses a progression of six training steps to teach the rodent the associated rules necessary to complete the full task. Task performance is typically measured by trials completed and by accuracy. Task accuracy can be evaluated across various spatial separations to engage hippocampal-dependent processes involved in spatial pattern separation. The latency between trial responses can also be evaluated, with food reward collection latency as a measure of motivation. The TUNL task can be used to assess working memory and cognitive deficits in rodent models with neurodegenerative and neurological disorders, providing a valuable tool to screen for new treatment options, in addition to assessing basic neurobiology.
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