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Title: The effects of [delta]-tetrahydrocannabivarin in an in vitro model of epileptiform activity and in vivo models of seizure
Author: Weston, Samantha Elizabeth
ISNI:       0000 0004 2726 6386
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2011
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Cannabis sativa has been used for symptomatic relief of seizures for thousands of years. The constituents responsible for such effects, their mechanisms and any involvement of the endocannabinoid system remain speculative. This work focussed on actions of the phytocannabinoid [delta]9-THCV on excitatory neurotransmission in in vitro cerebellar acute brain slices, an in vitro piriform cortical {PC} brain slice model of epileptiform activity and three in vivo rodent models of seizure. The functional effects of synthetic cannabinoids WIN55 (CBl/2R agonist) and AM251 (CBlR antagonist) and [delta]9-THCV on network level neurotransmission in the cerebellum were investigated using MEA extracellular electrophysiological recording methods. Significant increases from control level spontaneous spike firing rates recorded from Purkinje cells were seen upon addition of WIN 55 (5μM) and reversed by [delta]9-THCV {5 μML whilst significant spike firing rate reductions from control levels were induced by [delta]9-THCV (5 μM) or AM251 (2 μM). Functional effects of [delta]9-THCV and AM251 upon epileptiform activity in the Mg2+-free model of PC epileptiform activity were investigated using extracellular electrophysiological MEA recording techniques. Both [delta]9-THCV (>20μ M) and AM251 (>2 μM) significantly reduced burst complex incidence, paroxysmal depolarising shift (PDS) amplitude, PDS frequency and propagation rate across slices, effects which were reproduced following brain slice pre-incubation with [delta]9-THCV (10 μM) . Based on these results, potential anticonvulsant effects ; of [delta]9-THCV were investigated using pentylenetetrazole {PTZh pilocarpine (PIL)- and penicillin (PEN)- induced models of seizure. [delta]9-THCV was found to be significantly anticonvulsant in the PTZ-induced model. Results from other models demonstrated no significant anticonvulsant effect, but non- significant trends towards reduced percentage mortality, median severity and duration of seizures were seen. These results suggest that [delta]9-THCV has less anticonvulsant effect in a system with complete excitatory and inhibitory input. Further investigation is warranted to determine the cause of apparently conflicting results between in vitro and in vivo investigations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available