Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?

Abstract

Everyday, there are several millions of people that are increasingly unable to combat their frustrating and even fatal romance with getting high and/or experiencing "normal" feelings of well-being. In the USA, the FDA has approved pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement therapy. The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an increasing understanding of the intricate functions of brain reward circuitry through sophisticated neuroimaging and molecular genetic applied technology. Similar work is intensely investigated on a worldwide basis with enhanced clarity and increased interaction between not only individual scientists but across many disciplines. However, while it is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, there remains controversy regarding how to modulate its role clinically to treat and prevent relapse for both substance and non-substance-related addictive behaviors. While the existing FDA-approved medications promote blocking dopamine, we argue that a more prudent paradigm shift should be biphasic-short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward circuits.

Keywords: Agonistic therapy; Dopamine; Dopamine societies; Genetics and epigenetics; Reward deficiency syndrome (RDS).

Fig. 1

Schematic of the brain reward cascade: normal and abnormal representation. a The normal physiologic state of the neurotransmitter interaction at the mesolimbic region of the brain. Briefly, serotonin in the hypothalamus stimulates neuronal projections of methionine enkephalin in the hypothalamus that, in turn, inhibits the release of GABA in the substantia nigra, thereby allowing for the normal amount of dopamine to be released at the nucleus accumbens (NAc) reward site of the brain. b Hypodopaminergic function of the mesolimbic region of the brain. The hypodopaminergic state is due to gene polymorphisms as well as environmental elements (epigenetics), including both stress and neurotoxicity from aberrant abuse of psychoactive drugs (i.e., alcohol, heroin, cocaine, etc.) and genetic variables [2]