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| Content Provider | PubMed Central |
|---|---|
| Author | Mu, Ping Panksepp, Jaak Schlüter, Oliver Dong, Yan |
| Abstract | Dysregulation of excitatory synaptic input to nucleus accumbens (NAc) medium spiny neurons (MSNs) underlies a key pathophysiology of drug addiction and addiction-associated emotional and motivational alterations. Dynorphin peptides, which exhibit higher affinity to kappa type opioid receptors, are up-regulated within the NAc upon exposure to cocaine administration, and the increased dynorphin-signaling in NAc has been critically implicated in negative mood observed in cocaine- or stress-exposed animals. Despite such apparent behavioral significance of the NAc dynorphins, understanding of how dynorphins regulate excitatory synaptic transmission in NAc remains incomplete. Here, we focused on two key dynorphins, dynorphin A and B. Our current results show that dynorphin A and B differentially regulated excitatory postsynaptic currents (EPSCs) in NAc MSNs. Whereas perfusions of both dynorphin A and B to NAc slices decreased EPSCs in MSNs, the effect of dynorphin A, but not dynorphin B, was completely reversed by the kappa receptor-selective antagonist nor-Binaltorphimine. These results implicate kappa receptor-independent mechanisms in dynorphin B-mediated synaptic effect in NAc. Furthermore, repeated exposure to cocaine (15 mg/kg/day via intraperitoneal injection for 5 days, with 1 or 2 days withdrawal) completely abolished dynorphin A-mediated modulation of EPSCs in NAc MSNs, whereas the effect of dynorphin B remained largely unchanged. Given the quantitatively higher abundance of dynorphin B in the NAc, our present results suggest that the dynorphin B-mediated, kappa receptor-independent pathways predominate in the overall effect of dynorphins in cocaine-pretreated animals, and potentially in cocaine-induced alterations in mood. |
| Related Links | http://dx.doi.org/10.1016/j.biopsych.2010.09.014 |
| Ending Page | 235 |
| Page Count | 8 |
| Starting Page | 228 |
| File Format | |
| ISSN | 00063223 |
| e-ISSN | 18732402 |
| Journal | Biological psychiatry |
| Issue Number | 3 |
| Volume Number | 69 |
| Language | English |
| Publisher Date | 2011-02-01 |
| Access Restriction | Open |
| Subject Keyword | Biological Psychiatry Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biological Psychiatry |
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