On the early life origins of vulnerability to opioid addiction

Abstract

The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA interacts with factors such as increased access to opioids to directly influence brain development and function, and cause opioid addiction vulnerability, is unknown. We simulated ELA in female rats and this led to a striking opioid addiction-like phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of a less salient natural reward was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.

The Developmental Origins of Opioid Use Disorder and Its Comorbidities

“…This includes blunted sucrose and palatable food preference, reduced interest in social play, and decreased low-effort cocaine consumption (Molet et al, 2016 ; Bolton et al, 2018a , b ). In contrast, such anhedonia is not observed in female rats after LBN (Levis et al, 2019 ). Yet, others have identified an age-dependent reduction of sucrose preference and depressive-like behaviors in female mice (Goodwill et al, 2019 ).…”

“…Rather, in females, the prevailing phenotype includes the enhanced consumption of opioids (and other drugs of abuse) and palatable FIGURE 1 | Early life adversity (ELA) augments opioid-seeking behaviors and increases the demand for opioid drugs and highly palatable food. Adapted from Figures 1, 2 in Levis et al (2019). (A) Female LBN-experienced (ELA) rats trained to self-administer intravenous heroin engage in more persistent heroin-seeking behavior after the withdrawal of the drug and (B) augmented relapse induced by heroin-associated cues than their control (CTL) counterparts.…”

“…Using the LBN model of ELA, we have demonstrated that, while males develop anhedonia for natural rewards like social play, palatable food, and sucrose (Molet et al, 2016 ; Bolton et al, 2018a , b ), females developed a strikingly different phenotype ( Figure 1 ). LBN females exhibit a marked increase in addiction-like seeking for opioid drugs (Levis et al, 2019 ). These rats were resistant to the extinction of opioid-seeking behavior, had stronger cue-induced and heroin-primed reinstatement responses, and increased motivation to self-administer the opioid remifentanil in a translationally relevant task measuring economic demand (Treadway et al, 2009 ; Bentzley et al, 2013 ; Bickel et al, 2014 ), demonstrating a motivation to obtain the drug even at a very high cost.…”

Blocking CRH receptors in adults mitigates age-related memory impairments provoked by early-life adversity

“…Weaned males were housed with littermates of the same treatment group, three per cage. Female animals will be the focus of future studies [54]. The results from experiment 1 (Fig.…”

Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications

“…In humans, various forms of ELA are associated with illicit drug use later in life [ 21 , 22 , 23 ]. In addition, there are established links between ELA and obesity [ 21 , 24 ], however, the exact mechanisms are not understood.…”