The endogenous catecholamine norepinephrine (NE) exhibits anti-epileptic properties, however it is not well understood which adrenergic receptor (AR) mediates this effect. The aim of this study was to investigate alpha(1)-adrenergic receptor activation in region CA1 of the hippocampus, a subcortical structure often implicated in temporal lobe epilepsies. Using cell-attached and whole-cell recordings in rat hippocampal slices, we confirmed that selective alpha(1)-AR activation increases action potential firing in a subpopulation of CA1 interneurons. We found that this response is mediated via the alpha(1A)-AR subtype, initiated by sodium influx, and appears independent of second messenger signaling. In CA1 pyramidal cells, alpha(1A)-AR activation decreases activity due to increased pre-synaptic GABA and somatostatin release. Examination of post-synaptic receptor involvement revealed that while GABA(A) receptors mediate the majority of alpha(1A)-adrenergic effects on CA1 pyramidal cells, significant contributions are also made by GABA(B) and somatostatin receptors. Finally, to test whether alpha(1A)-AR activation could have potential therapeutic implications, we performed AR agonist challenges using two in vitro epileptiform models. When GABA(A) receptors were available, alpha(1A)-AR activation significantly decreased epileptiform bursting in CA1. Together, our findings directly link stimulation of the alpha(1A)-AR subtype to release of GABA and somatostatin at the single cell level and suggest that alpha(1A)-AR activation may represent one mechanism by which NE exerts anti-epileptic effects within the hippocampus.