Where Does Addiction Come From? Perspectives from the Past and Present

Editor’s note: It’s graduation season, which means a slew of new dissertations have been published. In today’s post, we include a few recent summaries of historical, psychological, and neurological perspectives on the etiology of addiction. These entries are part of an ongoing drug-related dissertation bibliography continuously compiled by Jonathon Erlen, selections of which were formerly published in the Social History of Alcohol and Drugs journal but are now periodically featured on the Points blog. Contact Dr. Erlen through the link above.

Intoxication and Empire: Distilled Spirits and the Creation of Addiction in the Early Modern British Atlantic
Author: Burton, Kristen D.
Abstract: This dissertation exams how the spread of imperialism in the British Atlantic led to the mass production and consumption of distilled spirits during the seventeenth and eighteenth centuries. Through transatlantic colonization, distilled liquors, once produced as medicinal remedies, developed into a thriving industry by the beginning of the eighteenth century. This change in the purpose and use of distilled spirits prompted political, religious, and medical leaders to ask new questions about the effects and possible threats of consuming such spirits. This dissertation is a study of perceptions; it examines how spirits became the means through which people evaluated the place and proper behavior of women, the working poor, indigenous peoples, enslaved laborers, and backcountry famers, among others. While alcohol was thought by many to be spiritually and physically nourishing, mass production and distribution of rum in the mid-seventeenth century created new questions and concerns among elites about intoxication, bodily health, and the perceived threat of lost control over the laboring poor in England, and over indigenous communities and enslaved peoples throughout the empire. Social elites constructed narratives around new notions of inebriation based upon the loss of physical, as well as moral, control. Through these narratives, physicians came to create new theories of habitual drinking as a compulsive act. Altered perceptions, constructed from unprecedented eighteenth-century drinking practices, redefined alcohol as an intoxicant. This established the framework of what became early addiction theory, which emerged during the initial decades of the modern era. Eighteenth-century imperial, medical, and religious debates over distilled spirits, in turn, established the foundation for early ideas of alcoholism and transatlantic movements advocating temperance.

Publication year: 2015
Advisor: Morris, Christopher C.
University/institution: The University of Texas at Arlington
Department: History

The Role of the Dopamine D1-D2 Receptor Heteromer in Brain Reward Function: Relevance to Drug Addiction and Depression
Author: Shen, Maurice Yen Fu
Abstract: We have identified a novel dopamine-mediated signaling complex, the D1-D2 receptor heteromer, which couples to Gq protein to elicit phospholipase C-mediated intracellular Ca2+ release. Activation of the D1-D2 heteromer was further shown to modulate the expression of proteins implicated in reward in the nucleus accumbens, such as calcium calmodulin kinase II (CaMKII) and brain derived neurotrophic factor (BDNF), a finding which may be of relevance in neuropsychiatric disorders that exhibit altered reward perception such as addiction and depression. Therefore, the purpose of current study was to investigate a role for the D1-D2 heteromer in reward-related behaviours using animal models of cocaine addiction and depression. The results show that D1-D2 heteromer stimulation by agonist SKF 83959 attenuated addiction-related behaviours including cocaine conditioned place preference (CPP), the maintenance and reinstatement of cocaine self-administration (SA), and the expression of locomotor sensitization to cocaine, whereas D1-D2 heteromer inactivation by a selective disrupting peptide TAT-D1 consistently augmented cocaine-induced behaviours, whereas a control scrambled peptide had no such effects. Moreover, D1-D2 heteromer stimulation alone was shown to induce conditioned place aversion, whereas its selective inactivation induced CPP. In the tests for depression, D1-D2 heteromer stimulation by SKF 83959 induced a pro-depressive and anxiogenic state in the forced swim test, novelty-induced hypophagia, and the elevated plus maze, effects that were abolished by pretreatment with TAT-D1 peptide. Lastly, it was shown that the D1-D2 heteromer exerts dual modulation on neuronal activity in certain regions of brain, increasing activity in the NAc, and exerting tonic inhibition in the prelimbic and infralimbic cortex, orbitofrontal cortex, lateral habenula, and the thalamus, which likely reflects the dual excitatory/inhibitory capabilities of the GABA/Glu-co-expressing D1R/D2R MSNs. Collectively, these findings indicate that the D1-D2 heteromer may be a single molecular entity that could bidirectionally modulate brain reward function depending on its state of activation. Such an unprecedented function of a receptor complex makes the D1-D2 heteromer an attractive and novel therapeutic target for cocaine addiction and major depression, two reward-related neuropsychiatric disorders that are currently without effective treatments.
Publication year: 2015
Advisor: George, Susan R.
Committee member: Fletcher, Paul J.; Nobrega, Jose N.
University/institution: University of Toronto (Canada)
Department: Pharmacology

The Role of Attachment to Parents in the Etiology of Substance Use Disorder

Author: Zhai, Zu Wei
Abstract: Substance Use Disorder (SUD) is a major public health problem costing over 500 billion dollars annually. An estimated 24.6 million Americans over age 12 were illicit drug users. 21.5 million are classified with dependence or abuse of alcohol and/or illicit drugs. Despite research efforts, the understanding of SUD etiology is still limited. Much research shows that SUD runs in families due to genetic and environmental contributions. Low attachment to parents, consequent to the chronic effects of parental SUD, may underlie the association between parents’ and offspring’s SUD. To date, limited research has been conducted to determine whether parent-child attachment bears on the relationship between SUD in parents and SUD risk in offspring. The aim of the current study was to determine the role of attachment to parents in the mechanism by which SUD in parents contributes to SUD risk in children. It was hypothesized that (1) parents’ substance use severity, among other SUD related variables, most consistently predicted substance involvement (substance use and SUD severity) in sons; (2) attachment to parents was associated with sons’ substance involvement, after accounting for parental substance use severity; (3) attachment to parents mediated and moderated the association between parents’ and sons’ substance use severity. Linear regression analysis determined that parental substance use severity was the most consistent predictor of sons’ substance involvement. Structural equation modeling showed that parental substance use severity mediated the association between parental SUD severity and sons’ substance use severity. After controlling for parental substance use severity and supervision, attachment to parents explained additional variance in sons’ substance involvement, and was associated with the onset rates of cannabis initiation, regular use, and problems with use. Structural equation modeling showed that attachment to fathers’ mediated the relationship between fathers’ and sons’ substance use severity, which leads to sons’ SUD. No significant moderation effects were found for attachment to parents. Attachment to parents also predicted illicit substance use at age 16. This study establishes that parent-child attachment is an integral factor in SUD etiology. Attachment based assessment and prevention tools may potentially improve clinical outcomes.
Publication year: 2015
Advisor: Tarter, Ralph E.
University/institution: University of Pittsburgh
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