In a groundbreaking study, scientists have pinpointed the neural pathway shared by addictive drugs like cocaine and morphine, shedding light on how these substances disrupt our natural cravings for essential needs such as food and water.
Researchers from Rockefeller University and the Icahn School of Medicine at Mount Sinai in New York utilized mouse models to investigate how morphine and cocaine affect brain reward circuits typically associated with hunger and thirst.
Lead researcher Jeffrey Friedman emphasizes the significance of their findings, stating, “We’ve known for decades that natural rewards, like food, and drugs can activate the same brain region. But what we’ve just learned is that they impact neural activity in strikingly different ways.”
The study employed advanced techniques such as whole-brain mapping, live imaging of neurons, and CRISPR-mediated genetic alterations to elucidate how addictive drugs ‘hijack’ natural reward pathways in the brain.
The nucleus accumbens (NAc), a crucial brain region involved in motivation and pleasure, was identified as a key player in both normal functions and drug rewards. Neurons projecting to the NAc from the orbitofrontal cortex were found to dampen the desire for natural rewards when activated by drug use.
Interestingly, cocaine and morphine exhibited distinct effects on the brain, with each activating specific subsets of neurons in the NAc. However, both drugs elicited stronger responses from overlapping neurons compared to natural rewards like food and water.
Over time, repeated drug exposure altered the behavior of mice, making them more interested in drugs and less interested in essential needs. This shift in behavior was accompanied by changes in neuron activity, particularly in response to natural rewards, resembling negative affective states observed during drug withdrawal.
Further analysis revealed a protein encoded by the Rheb gene that disrupts typical neuron communication, impacting how the brain processes rewards from food and water. Targeting pathways associated with this protein could offer new therapeutic avenues for addiction treatment.
Mount Sinai neuroscientist Eric Nestler underscores the importance of ongoing research in unraveling the intricate mechanisms underlying addiction, stating, “Understanding how addictive drugs can mess with a very well-coordinated system that normally connects physiological needs to appetite-related behavior, could mean we find better ways to manage addiction, which currently has few effective treatments.”
The study, published in Science, marks a significant step towards unraveling the complexities of addiction and holds promise for developing more effective interventions to combat substance abuse.
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