RATIONALE: A major problem in treating obesity is the high rate of relapse to abnormal food-taking behavior when maintaining diet. OBJECTIVES: The present study evaluates the reinstatement of extinguished palatable food-seeking behavior induced by cues previously associated with the palatable food, re-exposure to this food, or stress. The participation of the opioid and dopamine mechanisms in the acquisition, extinction, and cue-induced reinstatement was also investigated. MATERIALS AND METHODS: C57BL/6 mice were first trained on a fixed-ratio-1 schedule of reinforcement to obtain chocolate-flavored pellets during 20 days, which was associated to a stimulus light. Operant behavior was then extinguished during 20 daily sessions. mRNA levels of opioid peptide precursors and dopamine receptors were evaluated in the brain by in situ hybridization and RT-PCR techniques. RESULTS: A reinstatement of food-seeking behavior was only obtained after exposure to the food-associated cue. A down-regulation of prodynorphin mRNA was found in the dorsal striatum and nucleus accumbens after the acquisition, extinction, and reinstatement of the operant behavior. Extinction and reinstatement of this operant response enhanced proenkephalin mRNA in the dorsal striatum and/or the nucleus accumbens core. Down-regulation of D2 receptor expression was observed in the dorsal striatum and nucleus accumbens after reinstatement. An up-regulation of PDYN mRNA expression was found in the hypothalamus after extinction and reinstatement. CONCLUSIONS: This study provides a new operant model in mice for the evaluation of food-taking behavior and reveals specific changes in the dopamine and opioid system associated to the behavioral responses directed to obtain a natural reward.
RATIONALE: A major problem in treating obesity is the high rate of relapse to abnormal food-taking behavior when maintaining diet. OBJECTIVES: The present study evaluates the reinstatement of extinguished palatable food-seeking behavior induced by cues previously associated with the palatable food, re-exposure to this food, or stress. The participation of the opioid and dopamine mechanisms in the acquisition, extinction, and cue-induced reinstatement was also investigated. MATERIALS AND METHODS: C57BL/6 mice were first trained on a fixed-ratio-1 schedule of reinforcement to obtain chocolate-flavored pellets during 20 days, which was associated to a stimulus light. Operant behavior was then extinguished during 20 daily sessions. mRNA levels of opioid peptide precursors and dopamine receptors were evaluated in the brain by in situ hybridization and RT-PCR techniques. RESULTS: A reinstatement of food-seeking behavior was only obtained after exposure to the food-associated cue. A down-regulation of prodynorphin mRNA was found in the dorsal striatum and nucleus accumbens after the acquisition, extinction, and reinstatement of the operant behavior. Extinction and reinstatement of this operant response enhanced proenkephalin mRNA in the dorsal striatum and/or the nucleus accumbens core. Down-regulation of D2 receptor expression was observed in the dorsal striatum and nucleus accumbens after reinstatement. An up-regulation of PDYN mRNA expression was found in the hypothalamus after extinction and reinstatement. CONCLUSIONS: This study provides a new operant model in mice for the evaluation of food-taking behavior and reveals specific changes in the dopamine and opioid system associated to the behavioral responses directed to obtain a natural reward.
Authors: Ainhoa Plaza-Zabala; Elena Martín-García; Luis de Lecea; Rafael Maldonado; Fernando Berrendero Journal: J Neurosci Date: 2010-02-10 Impact factor: 6.167
Authors: Rudolph Spangler; Knut M Wittkowski; Noel L Goddard; Nicole M Avena; Bartley G Hoebel; Sarah F Leibowitz Journal: Brain Res Mol Brain Res Date: 2004-05-19
Authors: Ivan E de Araujo; Albino J Oliveira-Maia; Tatyana D Sotnikova; Raul R Gainetdinov; Marc G Caron; Miguel A L Nicolelis; Sidney A Simon Journal: Neuron Date: 2008-03-27 Impact factor: 17.173
Authors: Dennis R Sparta; Alice M Stamatakis; Jana L Phillips; Nanna Hovelsø; Ruud van Zessen; Garret D Stuber Journal: Nat Protoc Date: 2011-12-08 Impact factor: 13.491
Authors: Jenny L Wilkerson; Sudeshna Ghosh; Mohammed Mustafa; Rehab A Abdullah; Micah J Niphakis; Roberto Cabrera; Rafael L Maldonado; Benjamin F Cravatt; Aron H Lichtman Journal: Neuropharmacology Date: 2016-11-25 Impact factor: 5.250
Authors: Christian R Burgess; Yo Oishi; Takatoshi Mochizuki; John H Peever; Thomas E Scammell Journal: J Neurosci Date: 2013-06-05 Impact factor: 6.167
Authors: Javier Gutiérrez-Cuesta; Aurelijus Burokas; Samantha Mancino; Sami Kummer; Elena Martín-García; Rafael Maldonado Journal: Neuropsychopharmacology Date: 2014-06-19 Impact factor: 7.853