Beta-adrenergic receptors ([beta]-ARs) prime hippocampal synapses to stabilize long-term potentiation (LTP). This "metaplasticity" can persist for 1-2 h after pharmacologic activation of [beta]-ARs. It requires activation of PKA (cAMP-dependent protein kinase) during [beta]-AR priming. A-kinase anchoring proteins (AKAPs) tether PKA to downstream signaling proteins. We hypothesized that induction of this metaplasticity requires intact functioning of AKAPs. Acute application of stearated ht31, a membrane-permeant inhibitor of AKAPs, either during [beta]-AR activation 30 min prior to LTP induction or during LTP induction, attenuated the persistence of LTP. A control, inactive ht31 peptide did not affect [beta]-AR-mediated metaplasticity. These findings implicate PKA anchoring in the induction of [beta]-adrenergic metaplasticity of LTP.