Reconsolidation of a morphine place preference: impact of the strength and age of memory on disruption by propranolol and midazolam

Reactivation of memories may render them labile and subject to disruption by amnestic drugs thus reducing their impact on future behavior, but whether it is possible with well-established memories is not known. Here we examined the effect of two amnestic agents on reconsolidation of a conditioned place preference (CPP) for morphine when memory strength and memory age were varied. In a three-compartment apparatus animals received 4 or 8 experiences of morphine in one compartment and saline in the alternative compartment. The memory was then reactivated drug-free, and immediately afterwards animals received an injection of propranolol (10mg/kg, SC), midazolam (1mg/kg, IP), both amnestic agents combined, or saline. Animals conditioned with 4 pairings were re-tested 2 and 7 days after reactivation. After conditioning with 8 drug experiences memories were reactivated and treated 8 times, once every 48h, beginning 1 or 30 days after training. Propranolol, midazolam and their combination, disrupted reconsolidation for weak memories (4 pairings), but had little effect on stronger memories (8 pairings) reactivated 1 day after training. Extending the reactivation-amnestic treatments to 8 sessions did not disrupt the strong memory. Delaying reactivation sessions by 30 days enabled all three amnestic treatments to disrupt reconsolidation. Repeating amnestic treatment appeared to increase the effect of midazolam, but combining propranolol and midazolam did not enhance the amnestic effect. The amount of training and the age of the memory may be boundary conditions for reconsolidation.