Why does prolonged opioid use lead to drug cravings even after detoxification, despite dopamine receptor downregulation?

💡 Explanation

Glutamate-mediated plasticity plays a crucial role because long-term opioid use induces changes in glutamate transmission within the nucleus accumbens, strengthening synaptic connections related to drug-seeking behavior. Therefore, cravings persist even after dopamine pathways normalize, rather than being suppressed by GABA or other neurotransmitters.

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