Dopamine homeostasis brain functional connectivity in reward deficiency syndrome

Abstract

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors

“…Increased resting state functional connectivity as well as an increased neuronal recruitment has been demonstrated acutely on fMRI in both animal and humans within 15 (animal) to 60 (human) minutes post administration of neuro nutrient therapy. These studies demonstrate neuronal dopamine firing in brain areas involved in reward processing and possible induced neuroplasticity and “dopamine homeostasis” ( 37 , 38 ). The comprehensive role of dopamine as the mesolimbic system neurotransmitter underlying motivational function supports the low potency dopaminergic repletion therapy concept; sustainable, mild activation of D2 receptors ( 30 ).…”

Reward Deficiency Syndrome Solution Focused Brief Therapy to Begin Integrating the Sciences of Addiction & Reward Deficiency Syndrome (RDS)

“…RDSS include methods for achieving dopamine homeostasis [22]. RDSS also offers viable application for rejuvenating a brain damaged by toxicity, in neuro-nutrient supplements [23] which provide the amino acid building blocks for proper brain function, and pro-dopamine regulator therapy [24] to combat SUD.…”

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

“…Regarding both hoarding and shopping issues, the elimination of these unwanted behaviors in the patient is at the core of the mechanism of action of KB220Z. Previous work adequately showed not only selective DA activation across the brain reward circuitry ( Febo et al., 2017 ), but also evidence for DA homeostasis in protracted heroin dependence ( Blum, Febo, et al., 2017 ; Blum, Liu, et al., 2015 ).…”

“…In an animal study, Febo et al. ( 2017 ) illustrated the modulatory actions of a putative DA agonist (KB220Z) on the rsFC in association with a key region of the reward system, the NAc. The finding is that KB220Z, like optogenetic stimulation of the rat NAc ( Thanos et al., 2013 ), caused an increase in the connectivity between this central striatal reward structure and the dorsal hippocampus and anterior thalamus, areas crucial for cognition.…”

“…Even though there are, to date, 30 studies demonstrating the therapeutic and anti-addictive effects, there are none which demonstrate an anti-shopping or an anti-hoarding effect ( Febo et al., 2017 ). Moreover, this is the first report to ( Archer, Oscar-Berman, Blum, & Gold, 2013 ) describe the psychological effect of the patient’s ingestion of KB200z.…”