Drug-Induced Glucocorticoids and Memory for Substance Use

Abstract

The biological stress response of the body forms one of the foundations of adaptive behavior, including promoting (and impairing) different forms of memory. This response transcends stressful experiences and underlies reactions to challenges and even reinforcers such as addictive substances. Nevertheless, drug-induced stress responses are rarely incorporated into models of addiction. We propose here that drug-induced stress responses (particularly glucocorticoids) play a crucial role in addictive behavior by modulating the formation of memories for substance-use experiences. We review the contributions of amygdala-, striatum-, and hippocampus-based memory systems to addiction, and reveal common effects of addictive drugs and acute stress on these different memories. We suggest that the contributions of drug-induced stress responses to memory may provide insights into the mechanisms driving addictive behavior.

“Chasing the first high”: memory sampling in drug choice

“…Memories of past experiences can be brought to mind by incidental reminders, such as external stimulus (or internal stimulus [85,86] e.g., stress [6]). At a neural level, partial reactivation of activity patterns formed during the initial experience can lead to reactivation of all of the pattern.…”

“…When context memories are not recalled, decisions may be swayed by the first memory that comes to mind [18]. Suggestively, recent work has shown that memory recall prioritizes events with highly salient, surprising rewards [114][115][116]-which may describe early, positive drug experiences; and that stress may cue retrieval of past stressful occasionswhich, in SUD populations, may include or cause drug use [6,85]. Together, these findings support two routes by which acute stress may influence memory retrieval and yield relapse: (a) diminishing retrieval of drug-inconsistent context memories, leaving initial drug-related memories to guide behavior; and (b) promoting retrieval of drug-consistent context memories and hence drug memories themselves.…”

“…Yet despite empirical data showing that hippocampus and adjacent structures, which in humans are tightly linked to episodic memory, are critical to addiction-related behaviors [2][3][4], and recent work highlighting the role of drugs in memory encoding [5,6], the role of memory retrieval remains less well-understood, and potentially crucial [7][8][9][10].…”

Contribution of Dopamine Transporter Gene Methylation Status to Cannabis Dependency

“…As we demonstrated, this was the site that showed a significant difference in methylation status after the Bonferroni correction. This may be of vital importance since glucocorticoids mediate nervous system functions in substance dependency [ 35 ]. In response to this, we concluded that hindering glucocorticoid responses could change drug-induced reactions, including the modulation of drug-related learning and memory.…”

Vulnerability to relapse under stress: insights from affective neuroscience

“…An interesting recent account proposes that the influence of stress on substance-seeking behaviours could be circular [119,120]. We reviewed evidence suggesting that the stress-induced shift from goal-directed to habitual control relies on the activation of the glucocorticoid system [91][92][93][94], but strikingly, the consumption of addictive substances (e.g., nicotine, cannabis, alcohol, stimulants and opioids) increases the level of glucocorticoids (for a review see [119]). Although this substance-induced increase of glucocorticoid does not correlate with a subjective feeling of negative affect classically experienced under stress, it has been proposed that it contributes to the consolidation of cue-response memories supporting habitual learning and cue-affect memories supporting Pavlovian learning.…”