In substance addiction, drug-associated memories are known to powerfully compel craving and drug seeking behavior. Research by Prof. Barry Everitt at the University of Cambridge, UK, indicates that disrupting the brain’s memory pathways might point towards future addiction therapy approaches.
Everitt spoke as one of three awardees of the 2014 Fondation Ipsen Neuronal Plasticity Prize for outstanding contributions in the field of neuronal plasticity. At FENS, Europe’s largest neuroscience conference, he described research in rodents indicating that targeting ‘memory plasticity’ and thereby diminishing the impact of maladaptive drug memories might offer a key approach to future addiction treatment in humans.
Research teams led by Everitt have already established that the path to addiction entails several transitions, shifting behavioral control from one brain area to another – from voluntary, goal-directed action to involuntary, compulsive drug seeking habit. The recreational first stage involves reward stimulation controlled by the ventral striatum, the brain’s key reward-processing area. The addiction stage involves the establishment of automatic drug seeking habits that are powerfully elicited by drug-associated conditioned stimuli, and are controlled by the dorsal striatum.
Drug craving and seeking behavior, as well as relapse, are driven largely by recollection of powerful drug-associated memories, explained Everitt. As the brain retrieves these memories – by recall, or exposure to drug-related stimuli – memory reconsolidation takes place. This neurochemical process strengthens and reinforces memories, which can persistently impact behavior. “We specifically examined how we could target these maladaptive drug-related memories, and prevent them from triggering drug-taking and relapse,” he said.
Memory consolidation was previously assumed to be permanent, explained Everitt. But like many aspects of the brain, memory exhibits ‘plasticity,’ in its capacity to constantly rewire neural pathways, responding to changing stimuli and experiences by reorganizing brain connections. His research group uncovered that when drug memories are reactivated by retrieval, they enter a pliable and unstable state.
Taking advantage of this unstable state, Everitt’s Cambridge team found that in rats, memory reconsolidation could be prevented in one of two ways: by blocking brain chemicals, or by inactivating genes. In one study, the team diminished drug-seeking behaviors by obstructing a brain chemical receptor crucial to learning and memory, thus erasing memories. In another study, his team found they could weaken drug memories by altering a particular gene in the amygdala, a brain area processing emotional memory. In both studies, memory disruption only worked if the pathway was blocked at retrieval, during memory reconsolidation – at the moment before restabilization of the memory in the brain. Yet both methods seemed to weaken or erase maladaptive memories, and so reduced drug-seeking behavior and relapse.
These findings strongly suggest that the plasticity of memory reconsolidation is key to diminishing the impact of drug-associated recollections. “Of course, inactivating genes in the brain is not feasible in humans,” said Everitt. “So we’re directing our research to better identify the underlying brain mechanisms of memory reconsolidation.” Everitt believes that further research across these areas – including uncovering what might make some individuals more vulnerable – may enable development of medications tailored to chemically interrupt those memory processes in humans.
Treatments disrupting drug memories would need to be administered in a monitored clinical settings, while addicts reactivate their strongest drug memories, noted Everitt. But such therapies might not only help diminish drug-taking behaviors and relapse, they might also enhance abstinence-promoting treatment.
Additionally, memory reconsolidation treatment could also be relevant for other disorders involving maladaptive, unwanted memories, noted Everitt. “Persistent fear-related memories which greatly affect behavior – such as those in PTSD and other anxiety-related disorders – also hold potential for this type of treatment.”
Date: July 8, 2014