Journal article
Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine
Addiction biology, v 22(6), pp 1695-1705
Nov 2017
PMID: 27480648
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine
- Creators
- Jessica K Shaw - Drexel UniversityMark J Ferris - Wake Forest UniversityJason L Locke - Wake Forest UniversityZachary D Brodnik - Drexel UniversitySara R Jones - Wake Forest UniversityRodrigo A España - Drexel University
- Publication Details
- Addiction biology, v 22(6), pp 1695-1705
- Publisher
- Wiley
- Grant note
- R00 DA031791 / NIDA NIH HHS P50 DA006634 / NIDA NIH HHS R01 DA021325 / NIDA NIH HHS R01 DA030161 / NIDA NIH HHS KL2 TR001421 / NCATS NIH HHS R01 DA014030 / NIDA NIH HHS R01 DA031900 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000413904600019
- Scopus ID
- 2-s2.0-84980047561
- Other Identifier
- 991019167989004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Substance Abuse