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Molecular neurological correlates of endorphinergic/dopaminergic mechanisms in reward circuitry linked to endorphinergic deficiency syndrome (EDS)

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The consensus of the current literature strongly supports the concept that brain neurotransmitters, and second messengers involved in the net release of dopamine in the mesolimbic region, especially the Nucleus… Click to show full abstract

The consensus of the current literature strongly supports the concept that brain neurotransmitters, and second messengers involved in the net release of dopamine in the mesolimbic region, especially the Nucleus Accumbens (NAc), is directly linked to motivation, anti-stress, incentive salience (wanting), and well-being. The role of dopamine in terms of alcohol withdrawal symptomology, cocaine craving behavior, dopamine -condensation products (TIQs), and more recently, the genetic aspects of drug-seeking and pro-dopamine regulation, provide compelling evidence of the relevant molecular neurological correlates of dopaminergic /endorphinergic mechanisms in reward circuitry due to genetic polymorphisms and epigenetic insults. In the face of an Americans opioid epidemic, the clinical consensus is to treat Opioid Use Disorder (OUD) with life-long opioid substitution therapy. However, the authors suggest a paradigm shift involving novel modalities like targeting the endorphinergic system linked to dopamine release at the NAc, in terms of the induction of required "dopamine homeostasis." Utilizing the known genetic - environmental interaction theorem P = G +E, the authors provide a clear rationale for the adoption of genetic risk testing coupled with endorphinergic/dopamine regulation to address dysfunction across the brain reward circuitry. The goal of altering resting-state, functional connectivity may require a gentle "neurotransmitter fix" vis enkephalinase inhibition to overcome or combat - self-induction of acute dopamine release via psychoactive substance misuse resulting in chronic dopamine down-regulation. As subsets of reward deficiency, we are poised to provide novel, genetically guided therapy for endorphinergic, opioidergic, and dopaminergic deficiencies and related syndromes, utilizing "Precision Addiction Management.

Keywords: dopamine; reward circuitry; mechanisms reward; neurological correlates; molecular neurological

Journal Title: Journal of the Neurological Sciences
Year Published: 2020

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