Logo image
Back
The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system
Journal article   Open access   Peer reviewed

The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system

Rodrigo A España, Erik B Oleson, Jason L Locke, Bethany R Brookshire, David C S Roberts and Sara R Jones
The European journal of neuroscience, v 31(2), pp 336-348
Jan 2010
DOI: https://doi.org/10.1111/j.1460-9568.2009.07065.x
PMID: 20039943
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1111/j.1460-9568.2009.07065.xView
Published, Version of Record (VoR) Open

Abstract

Mesencephalon - metabolism Benzoxazoles - metabolism Limbic System - anatomy & histology Male Intracellular Signaling Peptides and Proteins - metabolism Limbic System - metabolism Mesencephalon - anatomy & histology Self Administration Urea - analogs & derivatives Mesencephalon - drug effects Urea - metabolism Dopamine - metabolism Limbic System - drug effects Orexins Receptors, Neuropeptide - antagonists & inhibitors Rats Neuropeptides - metabolism Orexin Receptors Random Allocation Rats, Sprague-Dawley Cocaine - administration & dosage Cocaine - pharmacology Animals Microdialysis Receptors, G-Protein-Coupled - antagonists & inhibitors Electrochemistry Signal Transduction - physiology Mice
Recent evidence suggests that the hypocretin-orexin system participates in the regulation of reinforcement processes. The current studies examined the extent to which hypocretin neurotransmission regulates behavioral and neurochemical responses to cocaine, and behavioral responses to food reinforcement. These studies used a combination of fixed ratio, discrete trials, progressive ratio and threshold self-administration procedures to assess whether the hypocretin 1 receptor antagonist, SB-334867, reduces cocaine self-administration in rats. Progressive ratio sucrose self-administration procedures were also used to assess the extent to which SB-334867 reduces responding to a natural reinforcer in food-restricted and food-sated rats. Additionally, these studies used microdialysis and in vivo voltammetry in rats to examine whether SB-334867 attenuates the effects of cocaine on dopamine signaling within the nucleus accumbens core. Furthermore, in vitro voltammetry was used to examine whether hypocretin knockout mice display attenuated dopamine responses to cocaine. Results indicate that when SB-334867 was administered peripherally or within the ventral tegmental area, it reduced the motivation to self-administer cocaine and attenuated cocaine-induced enhancement of dopamine signaling. SB-334867 also reduced the motivation to self-administer sucrose in food-sated but not food-restricted rats. Finally, hypocretin knockout mice displayed altered baseline dopamine signaling and reduced dopamine responses to cocaine. Combined, these studies suggest that hypocretin neurotransmission participates in reinforcement processes, likely through modulation of the mesolimbic dopamine system. Additionally, the current observations suggest that the hypocretin system may provide a target for pharmacotherapies to treat cocaine addiction.

Metrics

9 Record Views
205 citations in Web of Science
221 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Neurosciences
Logo image