glucocorticoids and b-adrenergic receptor activation could modulate amygdalar LTP. Experimental design: The effects of acute stress on BLA synaptic plasticity was studied in undisturbed control or restraint stressed mice. Next, the contribution of (i) corticosterone acting via the mineralocorticoid or glucocorticoid receptor (MR or GR) and (ii) b-adrenergic actions via the b2-adrenoceptor was investigated. Hereto, animals were pretreated intraperitoneally with the specific antagonists spironolactone (50mg/kg), mifepristone (10mg/kg) and propranolol (10mg/kg) respectively, or their vehicles. Thirty minutes later, animals were exposed to 20 min restraint stress or left undisturbed, subsequently decapitated after which brain slices were prepared for in vitro electrophysiological recordings. BLA field potentials were evoked 1−4 hours after stress via lateral amygdala stimulation. Subsequently, LTP was induced by applying high-frequency stimulation (100Hz, 1s) and recorded for 1 hr post-tetanus. Results: Compared to slices from non-stressed control mice, restraint stress effectively enhanced in vitro BLA LTP (response relative to pre-LTP baseline = 100%, mean±SEM: 142.1±5.9% vs 163.2±6.5%, p< 0.001), indicating increased synaptic strengthening after an acute emotional stressor. Next, we investigated the role of MR, GR and the b2-adrenoceptor in LTP formation of these mice. In undisturbed controls, mifepristone and propranolol did not influence LTP compared to vehicle. However, while initial responses remained unchanged, spironolactone gradually attenuated LTP (last 10 min, control: 135.4±2.6% vs spironolactone: 120.2±5.0%, p< 0.05), suggesting unstable LTP formation when MR is blocked. While initially reaching stressed control levels, similar attenuation with spironolactone was observed in stressed animals. Pretreatment with mifepristone resulted in very little LTP (stress/vehicle: 143.3±4.4% vs stress/mifepristone:117.2±4.0%, p< 0.05), suggesting that GR blockade not only prevented the stress-induced enhancement of LTP but attenuated LTP even beyond control levels. Propranolol decreased the initial stressinduced enhancement to control levels but also affected long-term LTP resulting in highly unstable synaptic strengthening. Conclusions: The present study shows that the BLA is highly sensitive to acute emotional stress, a situation that quickly and effectively increases LTP. Furthermore, the stress-induced strengthening in amygdalar plasticity seems to require both elevated central b-adrenergic signalling as well as corticosteroid actions. Although these systems affect LTP differently, they both seem to be critical in the formation of long-term stable emotional memory, even hours after the initial stress exposure. Reference(s)