Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors

Abstract

A memory trace in its active state is susceptible to interference by amnesic agents, such as hypothermia and electroconvulsive shock, and by NMDA receptor antagonists, suggesting that a time-dependent consolidation process occurs each time a memory is reactivated. The role of beta noradrenergic receptors in reconsolidation in rats was examined in both a positively reinforced radial maze task and a footshock-reinforced conditioned emotional response task. For the former, rats were trained over several days in a spatial reference memory task and received a single reactivation trial followed by propranolol. A temporally graded impairment was observed when propranolol treatment occurred after the memory reactivation trial. In the emotional task, memory impairing effects of propranolol were greater when the drug was administered after a reactivation trial than when administered immediately after the initial training. These results suggest that reactivation of memory triggers a beta receptor-dependent cascade of intracellular events, recapitulating that which occurs during initial postacquisition consolidation, thus permitting reorganization of the existing memory as a function of new information in the retrieval environment. This remarkable lability of an active memory trace provides a new basis for pharmacotherapeutic intervention in such syndromes as Posttraumatic Stress Disorder. beta adrenoreceptor antagonists may be promising pharmacological agents for attenuating debilitating memories at the time of their controlled reactivation.

Figures

Fig. 1.

Effect of propranolol at different time intervals after a reactivation trial in the radial maze task. Twenty-four hours after the reactivation session, control rats had good retention performance, whereas propranolol-injected rats (10 mg/kg, i.p.) showed amnesia when the injections were made up to 2 hr after the reactivation trial. **p < 0.01, significantly greater than saline group; ‡p < 0.05, significantly less than 5 min injection delay group.

Fig. 2.

Effect of propranolol on memory with or without reactivation trial. A, Rats received a propranolol injection (10 mg/kg, i.p.) in the animal vivarium 2 hr after a reactivation trial or after no reactivation trial (n = 14 in each group). There was a significant performance deficit in the group that had the reactivation trial before the drug treatment compared with the group that received drug alone. *p < 0.05. B, Procedure the same as in A, except that injections were made 5 min after a reactivation trial or in the vivarium (n = 8 in each group). There was a significant performance deficit in rats receiving the injection after a reactivation trial compared with those rats receiving drug treatment without reactivation. Note the nearly errorless performance of this group on the test trial. **p < 0.001.

Fig. 3.

Effect of propranolol on reward incentive. Latency (left) and total time (right) to consume five Chocopops before (white bars) and 24 hr after (black bars) injection of propranolol. There is no significant change in either measure (paired t test), indicating that the drug did not induce an aversion to the reinforcement.

Fig. 4.

Effect of propranolol injection 5 min after passive avoidance training. Left, Latency to place two paws into the dark box in the test session 48 hr after training. Propranolol (10 mg/kg, i.p.) significantly decreased this measure of retention. Right, Percentage of rats completely entering the dark box; there was no difference between control (n = 38) and propranolol-injected (n = 20) rats on this measure of retention.

Fig. 5.

Effect of propranolol 5 min after a reactivation in passive avoidance task. Left, Latency to place two paws in the shock compartment in the test session 48 hr after reactivation session. Propranolol-injected rats (10 mg/kg, i.p.) show a significant decrease in latency. Right, Percentage of rats completely entering the dark box. There was a significant increase in the propranolol-treated group on this measure of retention (control,n = 10; propranolol, n = 11; *p < 0.05). Note that only those rats treated with saline and showing perfect retention at the reactivation phase were used in this phase of the experiment, which accounts for the improvement in performance in saline-treated group shown here compared with Figure 4. Half were treated again with saline and half received propranolol after the reactivation trial.