Stress-dependent impairment of passive-avoidance memory by propranolol or naloxone

Abstract

Previous work has shown that the effect of opioid-receptor blockade on memory modulation is critically dependent upon the intensity of stress. The current study determined the effect of adrenergic-receptor blockade on memory modulation under varied levels of stress and then compared the effect of adrenergic-receptor blockade under intense stress to that of a) opioid-receptor blockade and b) concurrent opioid- and adrenergic-receptor blockade. In the first experiment, the β-adrenergic-receptor blocker propranolol impaired retention in the passive-avoidance procedure when administered immediately after exposure to intense stress (passive-avoidance training followed by swim stress) but not mild stress (passive-avoidance training alone). In the second experiment, while separate administration of either propranolol or the opioid-receptor blocker naloxone immediately after exposure to intense stress impaired retention, the combined administration of propranolol and naloxone failed to do so. These findings demonstrate that the effect of β-adrenergic-receptor blockade or opioid-receptor blockade on memory modulation in the passive-avoidance procedure is dependent upon the intensity of stress, and suggest that concurrent inactivation of endogenous adrenergic- and opioid-based memory modulation systems under stressful conditions is protective of memory.

Stress-dependent opioid and adrenergic modulation of newly retrieved fear memory

“…Finally, with regard to the effect of reactivation in the presence of pharmacological manipulation on subsequent retention 24 hr later, the results of the two experiments suggest that newly retrieved fear memory during reactivation, like newly acquired fear memory during consolidation (Schneider et al, 2009; Schneider et al, 2011), is modulated by stress-dependent activation of adrenergic and opioid systems. The finding that naloxone enhanced or impaired retention in a stress-dependent manner when administered after reactivation ( Experiment 1 ) — and that its effectiveness was dependent on the duration of reactivation—is consistent with a protective mechanism, mediated by endogenous opioids, that limits enhancement and impairment of newly retrieved memory under mild and intense stress, respectively.…”

“…The doses of propranolol and naloxone chosen were similar to doses that have previously been shown to be effective in studies on memory modulation (McGaugh, Introini-Collison, & Nagahara, 1988; Przybyslawski et al, 1999; Schneider et al, 2009; Schneider et al, 2011). …”

“…The second experiment (Experiment 2) was aimed at determining whether concurrent activation of endogenous opioid and adrenergic systems, like its effect on modulation of newly acquired fear memory in previous studies (Schneider et al 2011), limits impairment of newly retrieved fear memory under conditions of intense stress. Specifically, the effect of naloxone and propranolol, administered separately or in combination, on modulation of newly retrieved fear memory was determined under conditions of intense stress.…”

“…Recent studies on stress-dependent modulation of newly acquired fear memory in our laboratory, using ß-adrenergic and opioid-receptor blockers, have uncovered endogenous adrenergic and opioid based modulation systems, working in concert, that limit the strengthening or weakening of newly acquired fear memory during consolidation under conditions of mild or intense stress, respectively (Schneider et al, 2009; Schneider, Simson, Atapattu, & Kirby, 2011). The present study sought to determine if similar stress-dependent modulation, via adrenergic and opioid modulatory systems working concurrently, occurs during reconsolidation of newly retrieved fear memory.…”

“…In contrast to previous experiments on stress-dependent modulation of newly acquired memory in which the level of stress was manipulated shortly after training via stressors such as predator exposure (Diamond et al, 2006), restraint (Klenerova et al, 2003) or forced swim (Schneider et al, 2011), the present study focused on stress-dependent modulation of newly retrieved memory utilizing reactivation of the retrieved fear memory itself (24 hr after training) as the stressor. As an agent of stress, reactivated fear memory (freezing behavior) has been validated in studies using activation of the hypothalamo-pituitary- adrenal axis as a physiological index of stress intensity (Antoniadis & McDonald, 1999).…”