Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome

dopamineDopamine is crucial neurotransmitter and hormone in the body. This hormone serves many purposes. It plays a role in the pleasure and reward pathway of the brain as well as in memory and motor control. And any decline in this hormone presents the body with myriads of ill-health conditions. This hormone however is greatly affected by drugs of abuse, most drugs that are taken to produce induced euphoric feelings in a person works in such a manner that they increase the production of the dopamine neurotransmitter, when this neurotransmitter is produced up to certain levels it will get depleted in the long term and hence the problem sets in. Specifically, the euphoric properties of cocaine and other drugs of leisure lead to the development of chronic abuse, and appear to involve the acute activation of central dopamine (DA) neuronal systems. They proposed that DA depletion results from overstimulation of these neurons and excessive synaptic metabolism of the neurotransmitter. When this happens may suffer ill-health conditions. These may include; poor nutrition, stress, lack of sleep and the habitual use of antidepressants, symptoms such as depression, mood swings, poor attention and food cravings will also occur. Some of the major symptoms of dopamine deficiency are depression, chronic boredom, and a loss of satisfaction, apathy, chronic fatigue and low physical energy with no desire to exercise the body. To correct these problems, it is necessary for this hormone to be supplemented so that the normal levels are restored. In addicts the use of buprenorphine to treat opioid dependent individual is common and is approved by the FDA. While to many people it has been working well with many studies supporting its use has now been reported that using buprenorphine for a long time will jeopardize the life a person as cases of severe withdrawal symptoms have been common. Researchers have found it necessary to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes.

Researchers have currently proposed the use of dopamine agonists instead of antagonists like buprenorphine that is mostly used with naloxone can offer long term solution to dopamine deficiency. While it is well established that dopamine deficiency or a hypodopaminergic trait leads to aberrant substance seeking behaviors (RDS) and intact mu opiate receptors are important for maintaining “dopamine homeostasis”, scientists have suspected that opioid-dopaminergic interaction must be involved in buprenorphine response. In this regard they have provided some evidence that a putative dopamine agonist, KB220Z shows long-term potential as an opioid replacement compound especially in subjects having a genetically determined hypodopaminergic trait like RDS.

In a research study done by Kenneth Blum, Marlene Oscar-Berman, William Jacobs, Thomas McLaughlin and Mark S. Gold, it was found that dopamine genes can affect clinical outcomes in reward deficiency syndrome and therefore it is safe to use less powerful dopamine agonist dopaminergic genes in helping patients with low dopamine levels on a long-term basis.

Dopamine agonist therapy

Based on these earlier studies both Blum et al has continued to propose dopamine agonist therapy rather than dopamine antagonistic therapy currently favored by the approved FDA drugs as medical assisted treatment. Specifically, they proposed that D2 receptor stimulation can be accomplished via the use of KB220Z which is 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. In fact, this model has been proven in research showing DNA-directed compensatory overexpression which is a form of gene therapy of the DRD2 receptors, resulting in a significant reduction in alcohol as well as cocaine craving behavior in alcohol and cocaine preferring rodents.

This research done by Blum and his team suggested that utilizing less powerful dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a “wanting” messenger in the meso-limbic DA system. This team had a hypothesis that D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors.

dopamineAs revealed by the researchers stress and dopamine D2 receptor levels play a significant role in alcohol seeking behaviors. Another researcher Delis and his team observed that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood this also supports dopamine agonist therapy not antagonistic. It is therefore safe to use dopamine agonists instead of dopamine antagonists in treating those with low dopamine levels as they are much safer.

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Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome