Disruption of Maternal Parenting Circuitry by Addictive Process: Rewiring of Reward and Stress Systems

Addiction represents a complex interaction between the reward and stress neural circuits, with increasing drug use reflecting a shift from positive reinforcement to negative reinforcement mechanisms in sustaining drug dependence. Preclinical studies have indicated the involvement of regions within the extended amygdala as subserving this transition, especially under stressful conditions. In the addictive situation, the reward system serves to maintain habitual behaviors that are associated with the relief of negative affect, at the cost of attenuating the salience of other rewards. Therefore, addiction reflects the dysregulation between core reward systems, including the prefrontal cortex (PFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), as well as the hypothalamic–pituitary–adrenal axis and extended amygdala of the stress system. Here, we consider the consequences of changes in neural function during or following addiction on parenting, an inherently rewarding process that may be disrupted by addiction. Specifically, we outline the preclinical and human studies that support the dysregulation of reward and stress systems by addiction and the contribution of these systems to parenting. Increasing evidence suggests an important role for the hypothalamus, PFC, VTA, and NAc in parenting, with these same regions being those dysregulated in addiction. Moreover, in addicted adults, we propose that parenting cues trigger stress reactivity rather than reward salience, and this may heighten negative affect states, eliciting both addictive behaviors and the potential for child neglect and abuse

Synergy of Image Analysis for Animal and Human Neuroimaging Supports Translational Research on Drug Abuse

The use of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) in animal models of neuropathology is of increasing interest to the neuroscience community. In this work, we present our approach to create optimal translational studies that include both animal and human neuroimaging data within the frameworks of a study of post-natal neuro-development in intra-uterine cocaine-exposure. We propose the use of non-invasive neuroimaging to study developmental brain structural and white matter pathway abnormalities via sMRI and DTI, as advanced MR imaging technology is readily available and automated image analysis methodology have recently been transferred from the human to animal imaging setting. For this purpose, we developed a synergistic, parallel approach to imaging and image analysis for the human and the rodent branch of our study. We propose an equivalent design in both the selection of the developmental assessment stage and the neuroimaging setup. This approach brings significant advantages to study neurobiological features of early brain development that are common to animals and humans but also preserve analysis capabilities only possible in animal research. This paper presents the main framework and individual methods for the proposed cross-species study design, as well as preliminary DTI cross-species comparative results in the intra-uterine cocaine-exposure study

Cocaine exposure and children’s self-regulation: Indirect association via maternal aggression

Objectives: This study examined the association between prenatal cocaine exposure and children’s self-regulation at 3 years of child age. In addition to direct effects of prenatal cocaine exposure on children’s self-regulation, we hypothesized there would be indirect associations between cocaine exposure and self-regulation via higher maternal aggression and poor autonomic regulation in infancy. Methods: The sample consisted of 216 mother-infant dyads recruited at delivery from local area hospitals (116 cocaine exposed, 100 non-exposed). Infant autonomic regulation was measured at 7 months of age during an anger/frustration task, maternal aggression was coded from observations of mother-toddler interactions at 2 years of age, and children’s self-regulation was measured at 3 years of age using several laboratory paradigms. Results: Contrary to hypotheses, there were no direct associations between maternal cocaine use and children’s self-regulation. However, results from testing our conceptual model including the indirect effects via maternal aggression or infant parasympathetic regulation indicated that this model fit the data well, X2 (23) = 34.36, p > .05, Comparative Fit Index = .95, RMSEA = .05. Cocaine using mothers displayed higher intensity of aggression toward their toddlers during lab interactions across a variety of tasks at 2 years of age (β = .23, p < .05), and higher intensity of aggression at 2 years was predictive of lower self-regulation at 3 years (β = -.36, p < .01). Maternal cocaine use was also predictive of a non-adaptive increase in respiratory sinus arrythmia (RSA) from baseline to the negative affect task, but RSA change in infancy was not predictive of self-regulation at 3 years. Conclusions: Results are supportive of animal models indicating higher aggression among cocaine treated dams, and indicate that higher maternal aggression among cocaine using mothers is predictive of child self-regulatory outcomes over time