期刊
NEUROPSYCHOPHARMACOLOGY
卷 39, 期 4, 页码 989-999出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2013.299
关键词
cocaine; conditioned place preference; electrophysiology; Ca2+/calmodulin-dependent protein kinase II; synaptic plasticity; nucleus accumbens
资金
- National Institutes of Health [R01 DA024741, R21 MH095921, R01 NS081248, R21 DA036300, R0 DA026994]
- Clinical and Translational Science Award (CTSA) [UL1RR031973]
- National Center for Advancing Translational Sciences
Addictive drugs such as cocaine induce synaptic plasticity in discrete regions of the reward circuit. The aim of the present study is to investigate whether cocaine-evoked synaptic plasticity in the ventral tegmental area (VIA) and nucleus accumbens (NAc) is causally linked. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of long-term synaptic plasticity, learning, and drug addiction. We examined whether blocking CaMKII activity in the VIA affected cocaine conditioned place preference (CPP) and cocaine-evoked synaptic plasticity in its target brain region, the NAc. TatCN21 is a CaMKII inhibitory peptide that blocks both stimulated and autonomous CaMKII activity with high selectivity. We report that intra-VIA microinjections of tatCN21 before cocaine conditioning blocked the acquisition of cocaine CPP, whereas intra-VTA microinjections of tatCN21 before saline conditioning did not significantly affect cocaine CPP, suggesting that the CaMKII inhibitor blocks cocaine CPP through selective disruption of cocaine-cue-associated learning. Intra-VTA tatCN21 before cocaine conditioning blocked cocaine-evoked depression of excitatory synaptic transmission in the shell of the NAc slices ex vivo. In contrast, intra-VTA microinjection of tatCN21 just before the CPP test did not affect the expression of cocaine CPP and cocaine-induced synaptic plasticity in the NAc shell. These results suggest that CaMKII activity in the VIA governs cocaine-evoked synaptic plasticity in the NAc during the time window of cocaine conditioning.
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