Blockade of β1- but not of β2-adrenergic receptors replicates propranolol's suppression of the cerebral spread of an engram in mice

Abstract

Bitemporal injections of puromycin that primarily affect the hippocampal-entorhinal area induce amnesia of aversive maze-learning in mice for 3 days after training but are ineffective 6 or more days after training. At these later times, additional puromycin sites covering widespread forebrain areas are necessary to induce amnesia, a result that we attribute to the cerebral spread of the engram during the 6-day period. we have reported that blockade of about 60% of cerebral β-adrenergic receptors by a single, subcutaneous injection of (-)-propranolol, a nonselective β-receptor antagonist, inhibited engram spread for 60-90 days, at which time engram spread spontaneously occurred. In the present experiments using single doses of antagonists that appeared to block 60% of β2- or β1-adrenergic receptors, it was found that the selective β2 antagonist ICI 118,551 was without effect on engram spread, whereas the selective β1 antagonist betaxolol inhibited the spread for at least 3 months. Propranolol's effect consequently appears to be accounted for by its blockade of β1 receptors.