3 years ago

Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine

Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine
Sara R. Jones, Zachary D. Brodnik, Jessica K. Shaw, Jason L. Locke, Rodrigo A. España, Mark J. Ferris
The hypocretin/orexin (HCRT) system is implicated in reward and reinforcement processes through actions on the mesolimbic dopamine (DA) system. Here we provide evidence for the relationship between HCRT and DA in vivo in anesthetized and freely moving mice. The ability of cocaine to elicit reward-related behaviors in mice lacking the HCRT prepro-peptide (HCRT knock-out; KO) and wild-type controls was determined using conditioned place preference. Using a combination of microdialysis and in vivo fast scan cyclic voltammetry in anesthetized and freely moving mice, we investigated the underlying role of HCRT in the regulation of DA release and uptake. We show that, unlike wild-type mice, HCRT KO mice fail to develop characteristic conditioned place preference for cocaine. These mice also demonstrated reduced DA release and uptake under baseline conditions in both anesthetized and freely moving experiments. Further, diminished DA signaling in HCRT KO mice persists following administration of cocaine. These findings indicate that HCRT is essential for the expression of behaviors associated with the rewarding effects of cocaine, and suggest that HCRT regulation of reward and reinforcement may be related to disruptions to DA neurotransmission. The hypocretin/orexin system has been posited to influence reward and reinforcement processes through actions on the mesolimbic dopamine system. Using conditioned place preference, microdialysis, and fast-scan cyclic voltammetry, we demonstrate that hypocretin knockout mice fail to develop conditioned place preference for cocaine and display reduced dopamine release under baseline conditions and in response to cocaine.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/adb.12432

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