GABAergic drugs in WAG/Rij rats. Mechanisms underlying spike and wave discharges
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Promotor : Coenen, A.M.L. Co-promotor : Rijn, C.M. van
RU Radboud Universiteit Nijmegen, 7 februari 2006
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SubjectBiological psychology; Cognitive neuroscience; Biologische psychologie
It was aimed to further evaluate the role of the GABAergic neurotransmission system in the mechanisms underlying absence epilepsy. More specifically, the aim of this thesis is to investigate whether GABAergic neurotransmission is either quantitatively or qualitatively (or both) involved in the mechanisms underlying SWDs and whether this involvement is specifically determined by GABAA or GABAB mediated neurotransmission. To summarise, manipulation of different types of GABA receptors was shown to differentially affect the SWD activity. Systemic administration of GABA agonistic drugs resulted in an enhancement of SWD activity, with the exception of diazepam and loreclezole (discussed in 8.1.3.). It has been predicted that (relatively) enhancing GABAB-related neurotransmission in TC cells should slow down the peak frequency of SWDs (Destexhe, 1999; Destexhe and Sejnowski, 2003), which was confirmed in this thesis (chapter 4). Also, it was shown that hazard rate analysis can be a useful tool for hypothesising about the SWD starting and stopping mechanisms. Moreover, it was shown that this type of analysis might reveal more information on these mechanisms than the standard analysis of averages (of incidence and duration). In general, stimulation of GABAA receptors was shown to increase the probability of the generation of SWDs and to decrease the probability of the cessation of SWDs. Stimulation of GABAB receptors was also shown to increase the probability of SWD generation. Moreover, GABAB receptor activation not only decreased the probability of the stopping of a SWD, but also changed the course of this probability as the SWD lasts. Possible biological mechanisms responsible for these effects were discussed, and some possible types of drugs for the treatment of absence epilepsy were proposed.
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