Embryonic development and early gestation are critical times in which the developing fetus is highly susceptible to external toxins and environmental factors. The first sixty days of gestation often get overlooked because the woman is not aware she is pregnant (Adams, 2017). Examining the Behnke and Smith (2013) article on consequences of prenatal maternal substance abuse and the Hausknecht et. al. (2017) article on the impact of ethanol on the endocannabinoid system of the developing embryo, a synthesis of developmental and molecular structures affected by substance of abuse will be presented.
One of the central features of alcohol intoxication during pregnancy are the intellectual delays and associated brain dysfunctions. Prenatal alcohol exposure has long been associated with poor memory and executive functioning in the child (Behnke & Smith, 2013). These issues are coupled with dysfunctions in attention and emotional arousal in children suggesting disruptions in the prefrontal cortex and dopaminergic systems. Hausknecht et. al. (2017) present a specific look at one of the ways in which this dysregulation occurs in prenatal ethanol exposure via its impact on the endocannabinoid signaling in the ventral tegmental area’s dopamine neurons.
Behnke & Smith (2013) state that “mounting clinical data support an increased risk of ethanol abuse later in life after prenatal exposure.” As stated in lecture, a part of this is due to the release of endogenous endocannabinoids that flood the fetus through the placenta wall in response to alcohol (Adams, 2017). This flooding of CB1 receptors creates a downregulation of the receptor in the developing brain since the brain is in essence being fooled into thinking that this elevated level of CB1 receptor is normal (Hausknecht et. al., 2017). This creates alteration in what Hausknect et al. (2017) describe as the tonic signalling of eCB and results in abnormal homeostasis which permits persistent increases in excitatory synaptic strength.
In addition to being passed through the placenta wall, the harmful effects of ethanol can also be transferred from mother to child via breast milk (Behnke & Smith, 2013). According to the same authors, alcohol is concentrated heavily in human milk and heavy alcohol use can lead to reduced availability of milk and neurobehavioral delays in infancy and beyond. This is one of the ways in which the offspring can be effected. One of the ways in which eCB-LTD is impacted is by increased CP-AMPARs (calcium permeable AMPA receptors) which results in a decrease of glutamate and decreases signalling for LTD (Hausknecht et al., 2017). There is also a possible switch to LTP via suppression of NMDA-dependent LTP generation (Hausnecht et al, 2017).
The question then becomes if eCB over excitation and glutamate signalling decreases in the VTA are permanent and how the child may adapt. According to Heausnecht et al (2017) restoring eCB signaling in the dopamine neurons of the VTA could result in behavioral recovery if excitatory synapses are restored to a level of practical function. In terms of teratogens however, alcohol remains the primary cause of non-genetic intellectual disability (Behnke & Smith, 2013). Behnke and Smith (2013) also report that 10.8% of women drink during pregnancy and 3.7% binge drink. While much of this is due to early gestation and not being aware of the pregnancy, it has also been reported that women who drink heavily during pregnancy show poor habituation, low arousal levels, and motor abnormalities (Behnke & Smith, 2013). Clearly through overexcitation of eCB signalling and alterations in eCB-LTD their offspring show higher susceptibility not only to alcohol abuse but to other drugs of abuse such as methamphetamine.
Adams, J. (2017). Class lectures. UMass Boston.
Behnke, M., & Smith, V.C. (2013). Prenatal substance abuse: short- and long-term effects on the exposed fetus. American Academy of Pediatrics. 131(3). 1009-1017.
Haj-Dahmane, S., Hausknecht, K., Shen, R., Shen, Y., & Wang, R. (2017). Prenatal ehtanol exposure persistently alters endocannabinoid signaling and endocannabinoid-mediated excitatory synaptic plasticity in ventral tegmental area dopamine neurons. The Journal of Neuroscience. 37(24). 5798-5808.