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While metabolic reprogramming to glycolysis maintains short-term ATP supply, it leads to a long-term shortage of UDP-glucosamine (a substrate for matrix synthesis) and lactate accumulation, which can induce m collapse

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This in turn leads to increased genomic instability and a temporary increase of the mutation rate in DTPs, thus momentarily increasing the likelihood of resistance mechanisms being acquired 10,17,188 (Fig

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Finally, experiments conducted over the last three decades have repeatedly shown that disruption of dopaminergic transmission (via lesions or receptor blockade/silencing) has little or no effect on heroin or morphine self-administration in the rat [155,156,157,158,159,160,161,162,163]