Desynchronization of carbachol-induced theta-like activities by alpha-adrenergic agents in guinea pig hippocampal slices

The effect of alpha-adrenergic agents on theta-like activity (TLA) in guinea-pig hippocampal slices was studied. TLA was induced by a cholinergic agent, carbachol. TLA had a frequency of 4.66+/-0.08 Hz (mean+/-S.E.M.) and an amplitude of 96.3+/-8.3 microV in the dentate gyrus (DG). The alpha-adrenergic agents epinephrine and clonidine increased the frequency and decreased the amplitude of TLA in a concentration-dependent manner. The agents also increased antidromic and orthodromic population spike (PS) amplitudes of the granule cells, but did not have any effect on population EPSP. Another alpha-adrenergic agent, guanabentz, had the same effect as clonidine. The adenylate cyclase inhibitor SQ22536 suppressed the increase in PS amplitude by clonidine. The results suggest that these alpha2-adrenergic agents facilitate the activity of granule cells through the activation of the alpha2-adrenoreceptor and cAMP pathway, and the facilitation causes the desynchronization of TLA.