The contribution of GABAb circuits in the pro-epileptogenic action of nicotinic acetylcholine receptors in hippocampus

Nicotinic acetylcholine receptors (nAChRs) regulate epileptiform discharges generated by a number of
different pharmacological manipulations, in the hippocampus. Functional nicotinic receptor-mediated responses are most
prominently observed in hippocampal interneurons, however the pro-epileptogenic action of nAChRs appears to be independent of
fast GABAergic transmission since it is resistant to the blockade of GABAA receptors. To identify possible contribution of the
GABAB receptor in the nAChR-induced effect, a set of experiments was carried out in the presence of GABAB receptor antagonist
CGP55845A.
Material and Methods: Hippocampal slices (400µm thick) were prepared from male Wistar rats (3-4 weeks). Following a 1hr
equilibration in artificial cerebrospinal fluid, slices were transferred to a submerged-type recording chamber. Extracellular field
recordings were made in the Stratum pyramidale of the CA3 regions. Bath application of the convulsant compounds 4-aminopyridine
(4AP) or bicuculline resulted in the development of spontaneous epileptiform bursting.
Results: Slices pre-incubated with CGP55845A (GABAB receptor antagonist) were not able to exhibit burst frequency potentiation
of 4AP-induced epileptiform activity upon application of the selective nAChR agonist dimethylphenylpiperazinium iodide (DMPP; -
8.3  7%, n=11). Similarly, in the presence of CGP55845A, slices exhibited negligible burst frequency potentiation of bicucullineinduced epileptiform activity upon DMPP application (27.6  18%, n=9), in comparison to those observed in the absence of
CGP55845A (248  76 %, n=14). The suppression of epileptiform activity by the GABAB receptor agonist baclofen, was partially
recovered by subsequent co-application of DMPP (n=10).
Conclusion: These data suggests that nAChRs may regulate the excitability of hippocampal networks at least in part through
GABAB receptor-mediated mechanisms