Neurogenetics and neurobiology of dopamine in anhedonia

Abstract

Anhedonia, the inability to feel or experience pleasure, is a major problem for recovering addicts. Anhedonia can persist long after all traces of the offending drug are gone, and it can cause suicidal thinking and behaviors. We believe that anhedonia is not a distinct disorder but is a symptom of hypodopaminergic traits (genetic), epigenetic states, or a combination of the two. The 2011 endorsement of the American Society of Addiction Medicine’s new definition of addiction as a brain disorder has caught up with the science. Addiction involves an extended neuro-circuitry of the brain, and anhedonia is a condition that involves some of those same regions, including dopaminergic pathways in the mesocorticolimbic system. Andedonia, commonly reported by addicts in detox centers or early abstinence, may be directly tied to the drug-induced dopaminergic changes. It has been our position for decades that brain dopaminergic deficiencies result in reward- circuitry impairments, ultimately leading to Reward Deficiency Syndrome (RDS). The prefrontal cortex and cingulate gyrus contribute to drug relapse, and the nucleus accumbens (NAc) is a locus for craving behavior. While dopaminergic activity is very complex and may evoke differential physiological processes as it relates to pain and pleasure mechanisms (e.g., “liking” and “wanting”), anhedonic behavior has at its root a hypodopaminergic phenotype. In this chapter we discuss polymorphisms of reward genes in terms of inducing this hypodopaminergic phenotype (interaction of both genes and environment) and attempt to show their impact on the induction of anhedonia as a symptom of drug-induced withdrawal. Understanding of putative neurogenetic antecedents to RDS behaviors may provide a gene map for accessing the risk of an individual in developing anhedonia, especially following long-term drug abuse. We encourage the scientific community to carry on required studies to test this hypothesis. It is our belief that one mode of treatment to attenuate anhedonia is to provide natural activation of dopaminergic receptors (D2/D3) at the brain sites for craving and relapse in order to increase dopamine sensitivity.