Clock genes × stress × reward interactions in alcohol and substance use disorders

Abstract

Adverse life events and highly stressful environments have deleterious consequences for mental health. Those environmental factors can potentiate alcohol and drug abuse in vulnerable individuals carrying specific genetic risk factors, hence producing the final risk for alcohol- and substance-use disorders development. The nature of these genes remains to be fully determined, but studies indicate their direct or indirect relation to the stress hypothalamo-pituitary-adrenal (HPA) axis and/or reward systems. Over the past decade, clock genes have been revealed to be key-players in influencing acute and chronic alcohol/drug effects. In parallel, the influence of chronic stress and stressful life events in promoting alcohol and substance use and abuse has been demonstrated. Furthermore, the reciprocal interaction of clock genes with various HPA-axis components, as well as the evidence for an implication of clock genes in stress-induced alcohol abuse, have led to the idea that clock genes, and Period genes in particular, may represent key genetic factors to consider when examining gene × environment interaction in the etiology of addiction. The aim of the present review is to summarize findings linking clock genes, stress, and alcohol and substance abuse, and to propose potential underlying neurobiological mechanisms.

Dynamical state transitions into addictive behaviour and their early-warning signals

“…It has been shown that alcoholic patients experiencing alcohol withdrawal show disrupted sleep [ 38 ] and melatonin release [ 39 ], while in rodents, long-term alcohol intake and alcohol withdrawal have also been shown to affect circadian rhythms of drinking activity [ 40 , 41 ] and free wheel running activity [ 42 , 43 ]. In particular, in animals exposed to up to 20% alcohol solutions (but not when exposed to up to 10%), decreased circadian amplitudes were found during alcohol deprivation [ 40 , 44 ]. In this study, we used continuous measurements of locomotor activity, finding decreased circadian power during both deprivation and reintroduction phases ( figure 4 d ).…”

Brazilian cross-cultural adaptation and validation of the List of Threatening Events Questionnaire (LTE-Q)

“…The association with substance use provides a convergent validation to the tool, as it is in agreement with a large body of evidence, which shows the relationship between environmental stress and substance use disorders. 36,37 Experiencing adversity seems to be a risk factor for the development of addiction of other substances as well, such as methamphetamine, opiates, and nicotine. 38 It is agreed that physiological stress responses may lead to increased alcohol consumption and the search for other psychotropic substances in the pursuit of self-emotional regulation.…”

Physiological processes underlying organ injury in alcohol abuse

“…Within the alcohol field, the vast amount of research on clocks has largely focused on behavioral and neurobiological aspects of alcohol use. The circadian clock influences alcohol dependence and addictive behaviors (14,59,60). Associations also exist between alcohol consumption and clock disruption due to genetic or environmental factors.…”