Memory Systems of the Addicted Brain: The Underestimated Role of Drug-Induced Cognitive Biases in Addiction and Its Treatment

Abstract

Drug addiction may be viewed as a form of learning during which strong associations linking actions to drug-seeking are expressed as persistent stimulus–response habits, thereby maintaining a vulnerability to relapse. Disrupting cue–drug memory could be an efficient strategy to reduce the strength of cues in motivating drug-taking behavior. Upon reactivation, these memories undergo a reconsolidation process that can be blocked pharmacologically, providing an opportunity to prevent the powerful control of drug cues on behavior. This conceptually elegant approach still calls for more experimental data. However, an increasing body of evidence suggests that drug taking not only accelerates habit forming, but has long-lasting effects on interactions between memory systems eventually leading to a functional imbalance. The dorsal part of the striatum plays a critical role in habit/procedural learning, whereas the hippocampal memory system encodes relationships between events and their later flexible use. Both humans and rodents studies support the view that the hippocampus and the dorsal striatum interact in either a cooperative or competitive manner during learning, the prefrontal cortex being involved in the selection of an appropriate learning strategy. Chronic drug consumption biases normal interactions between these memory systems. For instance, drug-experienced rodents tend to use preferentially striatum-dependent learning strategies in navigational tasks. These persistent effects seem to occur at cellular, neurophysiological and behavioral levels to promote specific, striatal-dependent forms of learning, to the detriment of spatial/declarative, hippocampal-dependent and more flexible types of memory. Whether cue sensitive and response learners, in contrast to spatial learners, could be prone to drug addiction is an intriguing hypothesis which clearly deserves to be further explored. A loss of flexibility may be uncovered also by imposing changing rules on the subject, such as requiring an attentional shift between different perceptual features of a complex stimulus, as in the attentional set shifting task which was recently adapted to rodents. Working memory is at risk during transition phases, although it remains to be determined whether withdrawal-induced alterations are observed also during protracted abstinence. Drug-induced cognitive biases thus lead to cognitive rigidity which could play a critical, yet overlooked role in different phases of addiction (acquisition, extinction/withdrawal and relapse). They are also likely to preclude the clinical efficiency of treatments. Therefore, the aim of this research topic is to provide an overview of the current work investigating the long-term impact of drug use on learning and memory processes, how multiple memory systems modulate drug-seeking behavior, as well as how drug-induced cognitive biases could contribute to the persistence of addictive behaviors.