Research article summary (published 26 Jul 2009):

Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking.

Full Abstract

The orexin/hypocretin system has recently been implicated in reward-processing and addiction. We examined the involvement of the orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (4PT) prior to reinstatement testing. Male Sprague Dawley rats self-administered cocaine in 2-h sessions for 10 days, followed by extinction training. Reinstatement of cocaine-seeking was elicited by presentation of tone + light cues previously paired with cocaine infusions. SB (10, 20 and 30 mg/kg) dose-dependently decreased cue-induced reinstatement of cocaine-seeking without significantly affecting responding during late extinction. 4PT (10 and 30 mg/kg) did not significantly alter cue-induced reinstatement. In separate experiments, the highest doses of SB and 4PT had no significant effect on established cocaine self-administration, and 4PT reduced spontaneous activity in a locomotor test to a greater extent than SB. Finally, SB (30 mg/kg) had no effect on the acquisition of cocaine-paired cues during a Pavlovian cocaine-stimulus conditioning session in the operant chamber. Pretreatment with SB prior to the Pavlovian acquisition session had no effect on subsequent cue-induced reinstatement of cocaine-seeking elicited by those cues. However, pretreatment with SB prior to a second reinstatement session in the same animals significantly attenuated the expression of cue-induced reinstatement. These results show that orexin transmission at the orexin 1 receptor, but not the orexin 2 receptor, is necessary for the reinstatement of cocaine-seeking elicited by drug-paired cues and that orexin signaling is not critical for cocaine reinforcement or cocaine-stimulus conditioning.

Author information

Author/s: Smith, Rachel J (RJ); See, Ronald E (RE); Aston-Jones, Gary (G);

Affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425-5100, USA.

Grants: C06-RR015455 (Agency:NCRR NIH HHS) ; F31-DA019733 (Agency:NIDA NIH HHS) ; P50-DA015369 (Agency:NIDA NIH HHS) ; R01 DA017289-06 (Agency:NIDA NIH HHS) ; R01-DA017289 (Agency:NIDA NIH HHS) ; R37-DA06214 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2009-Aug; vol 30 (issue 3) : pp 493-503

Dates: Created 2009/08/18; Completed 2009/10/27; Revised 2009/11/03;

PMID: 19656173, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Behavior, Addictive - metabolism; physiopathology Benzoxazoles - pharmacology Brain - drug effects; physiology Cocaine - pharmacology Cocaine-Related Disorders - metabolism; physiopathology Cues Dopamine Uptake Inhibitors - pharmacology Extinction, Psychological - drug effects; physiology Intracellular Signaling Peptides and Proteins - metabolism

Intracellular Signaling Peptides and Proteins - metabolism Male Neuropeptides - metabolism Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled - metabolism Receptors, Neuropeptide - metabolism Reinforcement (Psychology) Signal Transduction - drug effects; physiology Urea - analogs & derivatives; pharmacology

Associated Chemicals: 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea (0) ; Benzoxazoles (0) ; Dopamine Uptake Inhibitors (0) ; Intracellular Signaling Peptides and Proteins (0) ; Neuropeptides (0) ; Receptors, G-Protein-Coupled (0) ; Receptors, Neuropeptide (0) ; orexin receptors (0) ; orexins (0) ; Cocaine (50-36-2) ; Urea (57-13-6)

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