Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

Abstract

Background and hypothesis: Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors,

The evolutionary roots of psychopathy

“…From an affective neuroscience perspective, it seems that the brain's mesolimbic system ("reward system" -linked to dopamine pathways) is crucial to the functioning of the drive system, regulating the pleasure response, i.e., the hedonic impact of the stimuli (Berridge & Kringelbach, 2008;Blum et al, 2008;Depue & Morrone-Strupinsky, 2005;Esch & Stefano, 2004). Further, it has been suggested that some genetic variations are also important in the function of the reward system, especially when linked to certain environmental experiences (Blum et al, 2008).…”

Hypothesizing Synergy between Acupuncture/ Auriculotherapy and Natural Activation of Mesolimbic Dopaminergic Pathways: Putative Natural Treatment Modalities for the Reduction of Drug Hunger and Relapse

“…We concluded that this seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results it is possible incorporate a safe, nonaddicting, natural dopaminergic receptor agonist that potentially up-regulates instead of downregulates dopaminergic receptors, preferably the D2 subtype (Blum et al, 2008).…”

Reward Deficiency Syndrome (RDS): Is there a Solution?

“…Specifically, Blum et al [34] proposed that D2 receptor stimulation can be accomplished via the use of KB220Z [35], a complex therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior.…”