Effect of early life social adversity on drug abuse vulnerability: Focus on corticotropin-releasing factor and oxytocin

Bardo, Michael T.; Hammerslag, Lindsey R.; Malone, Samantha G.

doi:10.1016/j.neuropharm.2021.108567

Cited by 24 publications

(16 citation statements)

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“…Oxytocin signaling in the medial prefrontal cortex has been reported to promote stress resilience in response to exposure to predictable maternal separation, while reduction in the expression of the oxytocin receptor has been shown to induce stress susceptibility in response to exposure to unpredictable maternal separation stress [ 172 ]. Early-life adversity has been shown to influence vulnerability to drug abuse by weakening oxytocin systems [ 173 ]. Early-life adversity disturbs the maturation of oxytocin neural circuits and produces long-lasting weakening of oxytocin systems [ 105 , 173 ].…”

Section: Resilience and Oxytocinmentioning

confidence: 99%

“…Early-life adversity has been shown to influence vulnerability to drug abuse by weakening oxytocin systems [ 173 ]. Early-life adversity disturbs the maturation of oxytocin neural circuits and produces long-lasting weakening of oxytocin systems [ 105 , 173 ]. Neonatal isolation has been reported to reduce partner preference in adult female prairie voles, and the social isolation-induced impairment in partner preference has been shown to be mitigated via pharmacological potentiation of oxytocin release by a melanocortin 3/4 agonist [ 174 ].…”

Section: Resilience and Oxytocinmentioning

confidence: 99%

“…Oxytocin has also been shown to be associated with drug vulnerability and alcohol dependence in adulthood. Oxytocin has been reported to reduce drug-abuse vulnerability via the oxytocin receptor in the NAc of adult animals [ 173 ]. Pair-housing with familiar mice has been shown to increase plasma oxytocin levels and to prevent social defeat-induced vulnerability to drug abuse [ 185 , 186 ].…”

Section: Resilience and Oxytocinmentioning

confidence: 99%

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Roles of Oxytocin in Stress Responses, Allostasis and Resilience

Takayanagi

Onaka

2021

IJMS

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Oxytocin has been revealed to work for anxiety suppression and anti-stress as well as for psychosocial behavior and reproductive functions. Oxytocin neurons are activated by various stressful stimuli. The oxytocin receptor is widely distributed within the brain, and oxytocin that is released or diffused affects behavioral and neuroendocrine stress responses. On the other hand, there has been an increasing number of reports on the role of oxytocin in allostasis and resilience. It has been shown that oxytocin maintains homeostasis, shifts the set point for adaptation to a changing environment (allostasis) and contributes to recovery from the shifted set point by inducing active coping responses to stressful stimuli (resilience). Recent studies have suggested that oxytocin is also involved in stress-related disorders, and it has been shown in clinical trials that oxytocin provides therapeutic benefits for patients diagnosed with stress-related disorders. This review includes the latest information on the role of oxytocin in stress responses and adaptation.

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Section: Resilience and Oxytocinmentioning

confidence: 99%

Section: Resilience and Oxytocinmentioning

confidence: 99%

Section: Resilience and Oxytocinmentioning

confidence: 99%

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Roles of Oxytocin in Stress Responses, Allostasis and Resilience

Takayanagi

Onaka

2021

IJMS

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“…Since early-life adversity is known to increase opioid self-administration, at least in part, by strengthening CRF modulation of HPA activity (Baracz et al, 2020; Bardo et al, 2021; Burke & Miczek, 2014; Walters & Kosten, 2019), the current project determined if intervention with PT150 following a two-hit model of developmental adversity (social isolation and acute stress) would reduce subsequent risk. As expected, in the absence of PT150 treatment, social isolation initiated at PND 21 increased overall adult fentanyl intake during initial 1-hr sessions, as well as during 6-hr sessions; however, the acute stress treatment did not add to the risk, even though it was shown to robustly increase plasma corticosterone levels.…”

Section: Discussionmentioning

confidence: 99%

“…There is high comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) in various populations (Dahlby & Kerr, 2020;Lo ´pez-Martínez et al, 2019). Extensive preclinical evidence shows that stressful PTSD-like events experienced during development increase drug self-administration and this increase in self-administration involves, at least in part, alterations in corticotrophin-releasing factor (CRF) regulation of the hypothalamicpituitary-adrenal (HPA) axis (Baracz et al, 2020;Bardo et al, 2021;Burke & Miczek, 2014;Walters & Kosten, 2019). This suggests the possibility that the increased risk for OUD resulting from early-life stressful events may be ameliorated by medications that normalize function of the HPA axis.…”

mentioning

confidence: 99%

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

Bardo¹,

Chandler²,

Denehy³

et al. 2023

Experimental and Clinical Psychopharmacology

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There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood. Rats were then treated daily with PT150 (50 mg/kg, oral) or placebo and were tested for acquisition of fentanyl self-administration in 1-hr sessions, followed by escalation across 6-hr sessions. Regardless of PT150 treatment or sex, acquisition of fentanyl self-administration in 1-hr sessions was greater in isolate-housed rats compared to social-housed rats; the acute stress manipulation did not have an effect on self-administration even though it transiently increased plasma corticosterone levels. During the 6-hr sessions, escalation of fentanyl was observed across all treatment groups; however, there was a significant PT150 Treatment × Sex interaction. While males self-administered more than females overall, PT150 decreased intake in males and increased intake in females, thus negating the sex difference. Although PT150 may serve as an effective treatment for reducing the risk of OUD following early-life stress in males, further work is needed to determine the mechanism underlying the differential effects of PT150 in males and females. Public Health SignificanceThe effect of the glucocorticoid receptor antagonist PT150 on fentanyl self-administration in male and female rats subjected to early-life stress was examined. Males self-administered more than females, but PT150 eliminated this sex difference, with intake decreasing in males and increasing in females. PT150 may be useful to treat opioid use disorder in males, but not in females.

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Considerations for Determining Whether Drug Addiction Is a Disability

Hirsch,

Mandel,

Hegmann

et al. 2023

Guides Newsletter

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There is an epidemic of drug overdose–related fatalities. Recent data indicate that the age-adjusted death rate from overdoses nearly quintupled over a 20-year period (2001-2021) to 32.4 per 100,000. More than 70% of these fatalities were caused by opioid overdose, especially the synthetic drug, fentanyl. Despite an increase in substance abuse and dependency treatment, mortality and morbidity associated with opioid, cocaine, psychostimulant, benzodiazepine, alcohol, and tobacco use disorders continue to rise. To better understand the factors contributing to this crisis, the multifaceted phenomenon of drug addiction is explored. The controversial chronic, relapsing “disease of the brain” model, which emphasizes the role of the neurotransmitter dopamine, the ventral tegmental area, and the nucleus accumbens, is critically considered. In addition, more expansive neurobiological models that include a host of other neurotransmitters, brain regions, and cognitive processes, as well as classical and operant conditioning and social learning theory to help better understand compulsive drug taking, tolerance, risk-taking, and relapse, were examined. For this, the roles of genetics and epigenetics vs individual agency in drug addiction were considered. The economic and occupational consequences borne both individually and societally are enormous. Ultimately, whether the presence of drug addiction satisfies the criteria for a disability remains a conundrum, especially from the perspectives of financial support (eg, Social Security, private insurance companies) vs regulation (eg, licensing agencies).

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Effect of early life social adversity on drug abuse vulnerability: Focus on corticotropin-releasing factor and oxytocin

Cited by 24 publications

References 273 publications

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

Considerations for Determining Whether Drug Addiction Is a Disability

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