Role of orexin/hypocretin in conditioned sucrose-seeking in rats

Angie M. Cason, Gary Aston Jones

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Rationale: The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. We reasoned that this system may be strongly engaged during periods of reward restriction, including food restriction. Objectives: This study examined the involvement of the orexin (Orx) system in responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed versus food-restricted male subjects. Methods: Sprague-Dawley rats (n = 108) were trained to self-administer sucrose, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) or progressive ratio (PR) sucrose self-administration, as well as on cue-induced reinstatement of sucrose-seeking. Finally, expression of the immediate early gene c-fos in Orx neurons was examined after self-administration, late extinction or cue-induced reinstatement of sucrose seeking. Results: SB decreased lever responding (by about 1/3) and the number of reinforcers earned during FR, and less so during PR, schedules and decreased cue-induced reinstatement to sucrose-seeking to extinction levels, predominately in food-restricted rats. Additionally, Fos expression in Orx neurons in perifornical and dorsomedial hypothalamus was increased during extinction. Conclusions: These results indicate that signaling at the OxR1 receptor is involved in pronounced sucrose reinforcement, and reinstatement of sucrose-seeking elicited by sucrose-paired cues, in food-restricted subjects. These findings lead us to conclude that conditioned activation of Orx neurons increases motivation for food reward during food restriction.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalPsychopharmacology
Volume226
Issue number1
DOIs
StatePublished - Mar 1 2013

Fingerprint

Sucrose
Food
Cues
Reward
Self Administration
Neurons
Orexins
Immediate-Early Genes
Hypothalamus
Sprague Dawley Rats
Motivation
Appointments and Schedules
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Addiction
  • Conditioned stimuli
  • Obesity
  • Orexin
  • Palatable food
  • Reward-based feeding

Cite this

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abstract = "Rationale: The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. We reasoned that this system may be strongly engaged during periods of reward restriction, including food restriction. Objectives: This study examined the involvement of the orexin (Orx) system in responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed versus food-restricted male subjects. Methods: Sprague-Dawley rats (n = 108) were trained to self-administer sucrose, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) or progressive ratio (PR) sucrose self-administration, as well as on cue-induced reinstatement of sucrose-seeking. Finally, expression of the immediate early gene c-fos in Orx neurons was examined after self-administration, late extinction or cue-induced reinstatement of sucrose seeking. Results: SB decreased lever responding (by about 1/3) and the number of reinforcers earned during FR, and less so during PR, schedules and decreased cue-induced reinstatement to sucrose-seeking to extinction levels, predominately in food-restricted rats. Additionally, Fos expression in Orx neurons in perifornical and dorsomedial hypothalamus was increased during extinction. Conclusions: These results indicate that signaling at the OxR1 receptor is involved in pronounced sucrose reinforcement, and reinstatement of sucrose-seeking elicited by sucrose-paired cues, in food-restricted subjects. These findings lead us to conclude that conditioned activation of Orx neurons increases motivation for food reward during food restriction.",
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Role of orexin/hypocretin in conditioned sucrose-seeking in rats. / Cason, Angie M.; Aston Jones, Gary.

In: Psychopharmacology, Vol. 226, No. 1, 01.03.2013, p. 155-165.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of orexin/hypocretin in conditioned sucrose-seeking in rats

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AU - Aston Jones, Gary

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AB - Rationale: The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. We reasoned that this system may be strongly engaged during periods of reward restriction, including food restriction. Objectives: This study examined the involvement of the orexin (Orx) system in responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed versus food-restricted male subjects. Methods: Sprague-Dawley rats (n = 108) were trained to self-administer sucrose, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) or progressive ratio (PR) sucrose self-administration, as well as on cue-induced reinstatement of sucrose-seeking. Finally, expression of the immediate early gene c-fos in Orx neurons was examined after self-administration, late extinction or cue-induced reinstatement of sucrose seeking. Results: SB decreased lever responding (by about 1/3) and the number of reinforcers earned during FR, and less so during PR, schedules and decreased cue-induced reinstatement to sucrose-seeking to extinction levels, predominately in food-restricted rats. Additionally, Fos expression in Orx neurons in perifornical and dorsomedial hypothalamus was increased during extinction. Conclusions: These results indicate that signaling at the OxR1 receptor is involved in pronounced sucrose reinforcement, and reinstatement of sucrose-seeking elicited by sucrose-paired cues, in food-restricted subjects. These findings lead us to conclude that conditioned activation of Orx neurons increases motivation for food reward during food restriction.

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