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Two animal studies explain why the relapse rate of cocaine use is so high.
In the study by Wang and colleagues, self-administration of cocaine for 5 days by adult rodents resulted in the generation by astrocytes of synapses that were initially inactive (silent) in the nucleus accumbens through the action of neuromodulators called thrombospondins (TSPs) acting on α2δ-1 receptors. Following withdrawal of cocaine, cocaine seeking and reinstatement of cocaine use in response to cues (e.g., a light). were driven by the new synapses, effects that could be blocked by gabapentin, which inhibits α2δ-1.
Jedema and colleagues allowed rhesus macaques to self-administer cocaine for 12 months; controls self-administered water. MRI-measured gray-matter dens…