Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling

Abstract

Prenatal neurodevelopment is dependent on precise functioning of multiple signalling pathways in the brain, including those mobilised by glucocorticoids (GC) and endocannabinoids (eCBs). Prenatal exposure to drugs of abuse, including opioids, alcohol, cocaine and cannabis, has been shown to not only impact GC signalling, but also alter functioning of the hypothalamic‐pituitary‐adrenal (HPA) axis. Such exposures can have long‐lasting neurobehavioural consequences, including alterations in the stress response in the offspring. Furthermore, cannabis contains cannabinoids that signal via the eCB pathway, which is linked to some components of GC signalling in the adult brain. Given that GCs are frequently used in pregnancy to prevent complications of prematurity, and also that rates of cannabis use in pregnancy are increasing, the likelihood of foetal co‐exposure to these compounds is high and may have additional implications for long‐term neurodevelopment. Here, we present a discussion of GC signalling and the HPA axis, as well as the effects of prenatal drug exposure on these pathways and the stress response, and we explore the interactions between GC and EC signalling in the developing brain and potential for neurodevelopmental consequences.

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats

“…It is reported that chronic alcohol exposure during pregnancy induces a reduction in ACTH basal levels while corticosterone secretion is not modified; besides, the exposure to some stressors induces an increase in corticosterone and CRH secretion, more than in controls (Lu et al, 2018 ). It is therefore reasonable to hypothesize that the stressful contingency of the MWM may boost the coping strategies of p-CAD progeny, by an “ ad hoc ” compensatory response of the HPA axis that makes p-CAD performance as “fair” as controls’ (Franks et al, 2020 ).…”

Becoming Stressed: Does the Age Matter? Reviewing the Neurobiological and Socio-Affective Effects of Stress throughout the Lifespan

“…It is well known that exposure to abuse drugs during the prenatal period can have long-lasting neurobehavioral consequences, including alterations in the offspring's stress response, in part due to alterations in the eCB system of the fetus [61]. Interestingly, several studies have demonstrated that stress exposure can have a similar impact on the eCB system to that described for prenatal exposure to abuse drugs.…”

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

“…Prenatal exposure to these substances can have a profound impact on adult offspring. It is well-established that substance use during pregnancy can negatively impact cognition ( 2 , 3 ), the stress response ( 4 ), anxiety ( 5 , 6 ), and susceptibility to drug addiction ( 7 , 8 ) in the adult offspring. These transgenerational effects involve epigenetic mechanisms (DNA methylation, histone acetylation, micro RNA) ( 9 – 11 ) as well as drug-induced changes in endocrine function ( 12 , 13 ), receptor expression ( 14 – 16 ), and structural changes within the brain ( 17 , 18 ) that can have pathological consequences extending into adulthood.…”