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Gene & Protein in Disease Dopaminergic dysfunction as pre-addiction

Figure 6. The first sub-genomic intelligence (SuGIN) between reward deficiency syndrome (RDS) as the central pre-addiction phenotype and other
pathways as endo-phenotypes. Nature refers to all outer stimuli influencing human cellular and molecular interactions. The human genome may prioritize
key chromosomes—here, we focus on the X and Y chromosomes—which, in turn, could influence autosomal chromosomes and numerous loci and genes.
Within this framework, eight endo-phenotypes are each strongly supported by evidence linking them to RDS at the core. The Genetic Addiction Risk
Severity test, developed by Blum et al., includes alleles from 10 genes. In the figure, arrows represent molecular interactions, while lines refer to the genes
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of the illustrated endo-phenotype(s). “Chr.” denotes chromosome, and stars highlight the endo-phenotypes. Additionally, X and Y refer to the respective
sex chromosomes. 51,52,57,58,75-77
and its broader impact on neuroplasticity and cellular imply beneficial effects of the secretome in terms of drug
responses to pain and opioid exposure. Key insights from dependence and self-administration.
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this work include: Finally, we developed a schematic (Figure 6) of our
(i) CeO serves as a potent tool for probing central pain overall genomic-based support for RDS as the central
mechanisms
(ii) The secretome can engage the opioid receptors pre-addiction phenotype and other pathways as endo-
typically affected by opioid drugs phenotypes, highlighting the importance of GARS
(iii) Treatment with buprenorphine followed by secretome testing.
leads to increased apoptosis compared to morphine 5. Conclusion
treatment
(iv) Both buprenorphine and secretome contribute to the If validated, these findings suggest that the true phenotype
enhanced maturation of glial cells is pre-addiction, characterized primarily by dopaminergic
(v) While opioids induced a marked acute elevation in dysregulation, while aging represents an endo-phenotype.
DA release, the secretome does not significantly alter Our analyses support the idea that the GARS test and an
DA levels compared to the control updated gene list along the pain-aging axis can identify
(vi) Following a five-day treatment with either secretome individuals who have risk alleles and are predisposed to
or opioids, there were no notable differences in addiction. Clinically, these insights can guide physicians,
synaptic markers. surgeons, and other clinical experts to prescribe the
Therefore, secretome may be an alternative to opioids precise drug(s) for pain relief with decreased risk of
in pain management. It appears to act on opioid receptors causing age-related phenotypes, including Alzheimer’s
but does not affect DA release, unlike morphine or and Parkinson’s disease. Furthermore, early identification
buprenorphine. This lack of impact on DA systems could of at-risk individuals through GARS testing could enable

Volume 4 Issue 3 (2025) 8 doi: 10.36922/gpd.8090