@article {2329,
	title = {α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse.},
	journal = {J Neurosci},
	volume = {34},
	number = {25},
	year = {2014},
	month = {2014 Jun 18},
	pages = {8605-11},
	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. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin{\textquoteright}s 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.},
	keywords = {Addictive, Animals, Behavior, Calcium Channels, Cocaine, Cocaine-Related Disorders, Male, nucleus accumbens, Rats, Recurrence, Self Administration, Sprague-Dawley, Synaptic Transmission},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.1204-13.2014},
	author = {Spencer, Sade and Brown, Robyn M and Quintero, Gabriel C and Kupchik, Yonatan M and Thomas, Charles A and Reissner, Kathryn J and Kalivas, Peter W}
}
