Dose-sensitive excitation and inhibition of spontaneous amygdala activity by propranolol

The effect of systemically administered propranolol was determined on spont aneous activity of neurons in the central nucleus (CeA) of the amygdala, a brain site implicated in fear-related learning and memory. Extracellular re cordings of single units in the CeA were obtained in vivo from rats adminis tered saline or the centrally and peripherally acting beta -adrenergic rece ptor blocker propranolol (4, 7, 10 mg/kg ip). The high dose (10 mg/kg) of p ropranolol markedly increased spontaneous activity of CeA neurons. In contr ast, the low (4 mg/kg) and intermediate (7 mg/kg) doses of propranolol sign ificantly decreased spontaneous CeA activity, with the suppressant effect o f propranolol on CeA firing rates weakening as the dosage increased from 3 to 7 mg/kg. These results suggest that (I) spontaneous activity of CeA neur ons is tonically influenced by competing excitatory and inhibitory modulato ry circuits, and (2) propranolol's effect on the two modulatory circuits is dose dependent, the high dose increasing spontaneous CeA activity by prefe rentially blocking an inhibitory circuit, the low dose decreasing spontaneo us CeA activity by preferentially blocking an excitatory circuit, and the i ntermediate dose weakly suppressing CeA activity by blocking both the excit atory and inhibitory modulatory circuits. Disinhibition of CeA activity by the high dose of propranolol may explain the enhancement of retention obser ved in the passive-avoidance task when this dose of the drug is administere d systemically, and may have implications for the use of propranolol clinic ally in treating aversive-memory-related anxiety disorders such as posttrau matic stress syndrome. (C) 2001 Elsevier Science Inc. All rights reserved.