Concurrent Inactivation Or Activation Of Opioid And Adrenergic Modulation Systems Under Stressful Conditions Protects Reactivated Fear Memory
Stress affects consolidation of memory via opposing action of inhibitory-opioid and excitatory-adrenergic modulation systems in brain sites such as the amygdala. In a previous study, we found that isolation of either modulation system--through pharmacological blockade of the other--impairs memory consolidation under stressful conditions, an effect not observed when both systems were concurrently blocked. These findings were taken as evidence that concurrent inactivation or activation of endogenous adrenergic- and opioid-based memory modulation systems under stressful conditions is protective of memory consolidation. In the present study we tested the hypothesis that a similar stress-induced modulation mechanism protects newly retrieved (i.e., reactivated) fear memory. Adrenergic and opioid modulation systems were pharmacologically blocked--either separately or in combination--immediately after reactivation of a stressful memory. Specifically, male, Long Evans rats underwent contextual-fear conditioning (foot-shock in a dark compartment) on Day 1, reactivation of fear memory (direct placement in the dark compartment for 120 sec in the absence of shock) on Day 2, and a 6 min retention test on Day 3. Immediately after direct placement on Day 2, the animals were divided into 4 groups that received vehicle, the opioid antagonist naloxone (3 mg/kg, i.p.), the ß-adrenergic blocker propranolol (10 mg/kg, i.p.) or a combination of naloxone and propranolol. Freezing as a measure of fear memory was monitored in 30 sec blocks during both reactivation and the retention test. The results showed that freezing was greater during the last 30 sec block than during the first 30 sec block on Day 2, indicating the increasingly stressful nature of the reactivation experience itself over time and suggesting that fear memory (and presumably stress) “incubates” during the reactivation session. While separate administration of either propranolol or naloxone immediately after reactivation on Day 2 impaired retention on Day 3, the combined administration of propranolol and naloxone failed to do so. These findings provide evidence that the simultaneous inactivation or activation of endogenous excitatory-adrenergic and inhibitory-opioid modulation systems under stressful conditions is protective of reactivated fear memory.
Society For Neuroscience 2011 Annual Meeting
November 12-16, 2011
Allen M. Schneider; Caitlin M. Daimon , '11; Jakob Mrozewski , '11; Nicholas M. Vogt , '12; John R. Keefe , '10; P. E. Simson; and L. G. Kirby.
"Concurrent Inactivation Or Activation Of Opioid And Adrenergic Modulation Systems Under Stressful Conditions Protects Reactivated Fear Memory".