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

The effect of systemically administered propranolol was determined on spontaneous activity of neurons in the central nucleus (CeA) of the amygdala, a brain site implicated in fear-related learning and memory. Extracellular recordings of single units in the CeA were obtained in vivo from rats administered saline or the centrally and peripherally acting beta-adrenergic receptor blocker propranolol (4, 7, 10 mg/kg i.p.). The high dose (10 mg/kg) of propranolol markedly increased spontaneous activity of CeA neurons. In contrast, the low (4 mg/kg) and intermediate (7 mg/kg) doses of propranolol significantly decreased spontaneous CeA activity, with the suppressant effect of propranolol on CeA firing rates weakening as the dosage increased from 4 to 7 mg/kg. These results suggest that (1) spontaneous activity of CeA neurons is tonically influenced by competing excitatory and inhibitory modulatory circuits, and (2) propranolol's effect on the two modulatory circuits is dose dependent: the high dose increasing spontaneous CeA activity by preferentially blocking an inhibitory circuit, the low dose decreasing spontaneous CeA activity by preferentially blocking an excitatory circuit, and the intermediate dose weakly suppressing CeA activity by blocking both the excitatory and inhibitory modulatory circuits. Disinhibition of CeA activity by the high dose of propranolol may explain the enhancement of retention observed in the passive-avoidance task when this dose of the drug is administered systemically, and may have implications for the use of propranolol clinically in treating aversive-memory-related anxiety disorders such as posttraumatic stress syndrome.