Received 5 May 2015, accepted for publication 27 July 2015

Background & Aims: 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 GABA_A receptors. To identify possible contribution of the GABA_B 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 (GABA_B 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 bicuculline-induced 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 GABA_B 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 GABA_B receptor-mediated mechanisms.