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• W2026006902 abstract "Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α₂δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α₂δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α₂δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α₂δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α₂δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. <i>In vivo</i>, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin9s effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α₂δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy." @default.
• W2026006902 created "2016-06-24" @default.
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• W2026006902 date "2014-06-18" @default.
• W2026006902 modified "2023-10-18" @default.
• W2026006902 title " 2 -1 Signaling in Nucleus Accumbens Is Necessary for Cocaine-Induced Relapse" @default.
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• W2026006902 doi "https://doi.org/10.1523/jneurosci.1204-13.2014" @default.
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