Document Detail


Differential orexin/hypocretin expression in addiction-prone and -resistant rats selectively bred for high (HiS) and low (LoS) saccharin intake.
MedLine Citation:
PMID:  22668854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rats that have been selectively bred for high (HiS) saccharin intake demonstrate elevated drug-seeking behavior in several phases of addiction compared to those bred for low (LoS) saccharin intake. HiS rats also consume greater amounts of highly palatable substances compared to LoS rats; however, little is known about the neurobiological substrates moderating the divergent behaviors found between the HiS and LoS lines. Orexins are neuropeptides that have been implicated in the conditioned cue aspects of drug abuse and overconsumption of palatable substances, and differential orexin activity in the HiS and LoS phenotypes may enhance our understanding of the close relationship between food and drug reward, and ultimately food and drug addiction. The lateral hypothalamus (LH) and perifornical area (PFA) are brain regions that have been implicated in regulating feeding behavior and addiction processes, and they contain orexinergic neurons that project broadly throughout the brain. Thus, we investigated orexin and c-Fos expression in the LH and PFA using immunohistochemistry in HiS and LoS rats following either control or cocaine (15 mg/kg) injections. Results indicated that HiS rats have higher orexin-positive cell counts compared to LoS rats in both the LH and PFA, regardless of cocaine (vs. saline) treatment. In contrast, neuronal activity indicated by c-Fos expression did not differ in either of these brain areas in HiS vs. LoS rats. These results suggest that the orexin system may be involved in aspects of genetically-mediated differences in vulnerability to compulsive, reward-driven behaviors.
Authors:
Nathan A Holtz; Natalie E Zlebnik; Marilyn E Carroll
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-02
Journal Detail:
Title:  Neuroscience letters     Volume:  522     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-11-09     Revised Date:  2013-10-30    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  12-5     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ireland Ltd.
Affiliation:
Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA. holt0324@umn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Breeding
Cell Count
Cocaine / pharmacology
Female
Food Preferences
Hypothalamus / cytology,  metabolism*
Intracellular Signaling Peptides and Proteins / metabolism*
Neurons / cytology,  metabolism
Neuropeptides / metabolism*
Proto-Oncogene Proteins c-fos / metabolism
Rats
Saccharin / pharmacology*
Species Specificity
Substance-Related Disorders / genetics*
Grant Support
ID/Acronym/Agency:
K05 DA015267/DA/NIDA NIH HHS; K05 DA15267/DA/NIDA NIH HHS; P20 DA024196/DA/NIDA NIH HHS; P20 DA024196/DA/NIDA NIH HHS; R01 DA003240/DA/NIDA NIH HHS; R01 DA003240/DA/NIDA NIH HHS; T32 GM008471/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Proto-Oncogene Proteins c-fos; 0/orexins; 50-36-2/Cocaine; 81-07-2/Saccharin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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