Blocking the increased reinforcing effects of cocaine induced by social defeat: Effects of palatable food
Keywords:
social defeat, male mice, cocaine, high-fat dietAbstract
Preclinical studies suggest that stimulation of the brain’s reward system by high-fat diets (HFD) could act as an alternative reinforcer. The main aim of the present study was to evaluate the effect of a limited and intermittent exposure to an HFD administered during and after exposure to Social Defeat (SD) on a non-effective dose of cocaine-induced Conditioned Place Preference (CPP). Experiment 1 consisted of modulating SD episodes with three different patterns of HFD access: 1h access before each session of SD; 2h access three days a week during the two weeks of SD exposure; and 2h access 4h after each SD. Experiment 2 consisted of modulating the effects of stress on CPP acquisition with three patterns of HFD access: 1h access before each conditioning session; 2h access three days a week throughout the two-week period of the CPP; and 2h access three days a week from the last SD episode to the end of CPP. HFD administered during the period of SD episodes counteracted the increased sensitivity that SD produces on the reinforcing effects of cocaine. Access to HFD before the conditioning session or three days a week (CPP-SD-MWF) during the acquisition of CPP blocked this increased sensitivity. In the striatum, SD induced a decrease in the cannabinoid 1 receptor (Cb1r) gene expression, not affected by HFD, and increased corticotrophin releasing hormone receptor 1 (Crhr1) gene expression, except for those mice fed on HFD after SD encounters. Our findings indicate that a small intake of HFD may attenuate the social stress–induced increase in the rewarding properties of cocaine.References
Arenas, M. C., Pérez-Esteban, I., Cañeque-Rufo, H., Gramage, E., Herradón, G. y Rodríguez-Arias, M. (2025). Intermittent and limited exposure to a high-fat diet prevents social defeat-induced increase in ethanol intake and neuroinflammation. Food & Function, 16(12), 5133–5150. https://doi.org/10.1039/D5FO00584A
Auvinen, H. E., Romijn, J. A., Biermasz, N. R., Pijl, H., Havekes, L. M., Smit, J. W. A., Rensen, P. C. N. y Pereira, A. M. (2012). The effects of high fat diet on the basal activity of the hypothalamus–pituitary–adrenal axis in mice. Journal of Endocrinology, 214(2), 191–197. https://doi.org/10.1530/JOE-12-0056
Avena, N. M., Rada, P. y Hoebel, B. G. (2008). Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience & Biobehavioral Reviews, 32(1), 20–39. https://doi.org/10.1016/j.neubiorev.2007.04.019
Baladi, M. G., Daws, L. C. y France, C. P. (2012). You are what you eat: Influence of type and amount of food consumed on central dopamine systems and the behavioral effects of direct- and indirect-acting dopamine receptor agonists. Neuropharmacology, 63(1), 76–86. https://doi.org/10.1016/j.neuropharm.2012.02.005
Ballestín, R., Alegre-Zurano, L., Ferrer-Pérez, C., Cantacorps, L., Miñarro, J., Valverde, O. y Rodríguez-Arias, M. (2021). Neuroinflammatory and behavioral susceptibility profile of mice exposed to social stress towards cocaine effects. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 105, 110123. https://doi.org/10.1016/j.pnpbp.2020.110123
Barson, J. R., Morganstern, I. y Leibowitz, S. F. (2012). Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use. ILAR Journal, 53(1), 35–58. https://doi.org/10.1093/ilar.53.1.35
Bello, N. T., Coughlin, J. W., Redgrave, G. W., Ladenheim, E. E., Moran, T. H. y Guarda, A. S. (2012). Dietary conditions and highly palatable food access alter rat cannabinoid receptor expression and binding density. Physiology & Behavior, 105(3), 720–726. https://doi.org/10.1016/j.physbeh.2011.09.021
Blanco-Gandía, M. C., Aracil-Fernández, A., Montagud-Romero, S., Aguilar, M. A., Manzanares, J., Miñarro, J. y Rodríguez-Arias, M. (2017c). Changes in gene expression and sensitivity of cocaine reward produced by a continuous fat diet. Psychopharmacology, 234(15), 2337–2352. https://doi.org/10.1007/s00213-017-4630-9
Blanco-Gandía, M. C., Cantacorps, L., Aracil-Fernández, A., Montagud-Romero, S., Aguilar, M. A., Manzanares, J., Valverde, O., Miñarro, J. y Rodríguez-Arias, M. (2017a). Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice. Neuropharmacology, 113, 31–44. https://doi.org/10.1016/j.neuropharm.2016.09.020
Blanco-Gandía, M. C., Ledesma, J. C., Aracil-Fernández, A., Navarrete, F., Montagud-Romero, S., Aguilar, M. A., Manzanares, J., Miñarro, J. y Rodríguez-Arias, M. (2017b). The rewarding effects of ethanol are modulated by binge eating of a high-fat diet during adolescence. Neuropharmacology, 121, 219–230. https://doi.org/10.1016/j.neuropharm.2017.04.040
Blanco-Gandía, M. C., Miñarro, J. y Rodríguez-Arias, M. (2019). Behavioral profile of intermittent vs continuous access to a high fat diet during adolescence. Behavioural Brain Research, 368, 111891. https://doi.org/10.1016/j.bbr.2019.04.005
Blanco-Gandía, M. C., Montagud-Romero, S., Aguilar, M. A., Miñarro, J. y Rodríguez-Arias, M. (2018). Housing conditions modulate the reinforcing properties of cocaine in adolescent mice that binge on fat. Physiology & Behavior, 183, 18–26. https://doi.org/10.1016/j.physbeh.2017.10.014
Boyson, C. O., Holly, E. N., Shimamoto, A., Albrechet-Souza, L., Weiner, L. A., DeBold, J. F. y Miczek, K. A. (2014). Social Stress and CRF–Dopamine Interactions in the VTA: Role in Long-Term Escalation of Cocaine Self-Administration. The Journal of Neuroscience, 34(19), 6659–6667. https://doi.org/10.1523/JNEUROSCI.3942-13.2014
Buchanan, T. W. y Lovallo, W. R. (2019). The role of genetics in stress effects on health and addiction. Current Opinion in Psychology, 27, 72–76. https://doi.org/10.1016/j.copsyc.2018.09.005
Burke, A. R., DeBold, J. F. y Miczek, K. A. (2016). CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: Prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence. Psychopharmacology, 233(14), 2727–2736. https://doi.org/10.1007/s00213-016-4336-4
Burke, A. R. y Miczek, K. A. (2015). Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: Role of social experience and adaptive coping behavior. Psychopharmacology, 232(16), 3067–3079. https://doi.org/10.1007/s00213-015-3947-5
Burke, A. R., Watt, M. J. y Forster, G. L. (2011). Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression. Neuroscience, 197, 269–279. https://doi.org/10.1016/j.neuroscience.2011.09.008
Carnevali, L., Montano, N., Tobaldini, E., Thayer, J. F. y Sgoifo, A. (2020). The contagion of social defeat stress: Insights from rodent studies. Neuroscience & Biobehavioral Reviews, 111, 12–18. https://doi.org/10.1016/j.neubiorev.2020.01.011
Coccurello, R., Romano, A., Giacovazzo, G., Tempesta, B., Fiore, M., Giudetti, A. M., Marrocco, I., Altieri, F., Moles, A. y Gaetani, S. (2018). Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat. European Journal of Nutrition, 57(4), 1485–1498. https://doi.org/10.1007/s00394-017-1434-y
Covington, H. y Miczek, K. (2001). Repeated social-defeat stress, cocaine or morphine. Psychopharmacology, 158(4), 388–398. https://doi.org/10.1007/s002130100858
Cristino, L., Becker, T. y Di Marzo, V. (2014). Endocannabinoids and energy homeostasis: An update. BioFactors, 40(4), 389–397. https://doi.org/10.1002/biof.1168
Dallman, M. F., Pecoraro, N., Akana, S. F., la Fleur, S. E., Gomez, F., Houshyar, H., Bell, M. E., Bhatnagar, S., Laugero, K. D. y Manalo, S. (2003). Chronic stress and obesity: A new view of “comfort food.” Proceedings of the National Academy of Sciences, 100(20), 11696–11701. https://doi.org/10.1073/pnas.1934666100
Davis, J. F., Tracy, A. L., Schurdak, J. D., Tschöp, M. H., Lipton, J. W., Clegg, D. J. y Benoit, S. C. (2008). Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. Behavioral Neuroscience, 122(6), 1257–1263. https://doi.org/10.1037/a0013111
Daws, L. C., Avison, M. J., Robertson, S. D., Niswender, K. D., Galli, A. y Saunders, C. (2011). Insulin signaling and addiction. Neuropharmacology, 61(7), 1123–1128. https://doi.org/10.1016/j.neuropharm.2011.02.028
Del Olmo, N., Blanco-Gandía, M. C., Mateos-García, A., Del Rio, D., Miñarro, J., Ruiz-Gayo, M. y Rodríguez-Arias, M. (2019). Differential Impact of Ad Libitum or Intermittent High-Fat Diets on Bingeing Ethanol-Mediated Behaviors. Nutrients, 11(9), 2253. https://doi.org/10.3390/nu11092253
de Macedo, I. C., de Freitas, J. S. y da Silva Torres, I. L. (2016). The Influence of Palatable Diets in Reward System Activation: A Mini Review. Advances in Pharmacological Sciences, 2016, 1–7. https://doi.org/10.1155/2016/7238679
Dickerson, S. S. y Kemeny, M. E. (2004). Acute Stressors and Cortisol Responses: A Theoretical Integration and Synthesis of Laboratory Research. Psychological Bulletin, 130(3), 355–391. https://doi.org/10.1037/0033-2909.130.3.355
DiLeone, R. J., Taylor, J. R. y Picciotto, M. R. (2012). The drive to eat: Comparisons and distinctions between mechanisms of food reward and drug addiction. Nature Neuroscience, 15(10), 1330–1335. https://doi.org/10.1038/nn.3202
Erhardt, E., Zibetti, L. C. E., Godinho, J. M., Bacchieri, B. y Barros, H. M. T. (2006). Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin. Brazilian Journal of Medical and Biological Research, 39(12), 1625–1635. https://doi.org/10.1590/S0100-879X2006001200014
Esch, T., Stefano, G. B. y Michaelsen, M. M. (2024). The foundations of mind‐body medicine: Love, good relationships, and happiness modulate stress and promote health. Stress and Health, 40(4). https://doi.org/10.1002/smi.3387
Ferrer-Pérez, C., Reguilón, M. D., Manzanedo, C., Aguilar, M. A., Miñarro, J. y Rodríguez-Arias, M. (2018). Antagonism of corticotropin-releasing factor CRF 1 receptors blocks the enhanced response to cocaine after social stress. European Journal of Pharmacology, 823, 87–95. https://doi.org/10.1016/j.ejphar.2018.01.052
Ferrer-Pérez, C., Reguilón, M. D., Manzanedo, C., Miñarro, J. y Rodríguez-Arias, M. (2019). Social Housing Conditions Modulate the Long-Lasting Increase in Cocaine Reward Induced by Intermittent Social Defeat. Frontiers in Behavioral Neuroscience, 13. https://doi.org/10.3389/fnbeh.2019.00148
Foster, M. T., Warne, J. P., Ginsberg, A. B., Horneman, H. F., Pecoraro, N. C., Akana, S. F. y Dallman, M. F. (2009). Palatable Foods, Stress, and Energy Stores Sculpt Corticotropin-Releasing Factor, Adrenocorticotropin, and Corticosterone Concentrations after Restraint. Endocrinology, 150(5), 2325–2333. https://doi.org/10.1210/en.2008-1426
Friuli, M., Eramo, B., Sepe, C., Kiani, M., Casolini, P. y Zuena, A. R. (2025). The endocannabinoid and paracannabinoid systems in natural reward processes: Possible pharmacological targets? Physiology and Behavior, 296. https://doi.org/10.1016/j.physbeh.2025.114929
Gemesi, K., Holzmann, S. L., Kaiser, B., Wintergerst, M., Lurz, M., Groh, G., Böhm, M., Krcmar, H., Gedrich, K., Hauner, H. y Holzapfel, C. (2022). Stress eating: An online survey of eating behaviours, comfort foods, and healthy food substitutes in German adults. BMC Public Health, 22(1), 391. https://doi.org/10.1186/s12889-022-12787-9
Giménez-Gómez, P., Ballestín, R., Gil de Biedma-Elduayen, L., Vidal, R., Ferrer-Pérez, C., Reguilón, M. D., O’Shea, E., Miñarro, J., Colado, M. I. y Rodríguez-Arias, M. (2021). Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine reward. Neuropharmacology, 197, 108753. https://doi.org/10.1016/j.neuropharm.2021.108753
Gobbi, G., Bambico, F. R., Mangieri, R., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M. G., Debonnel, G., Duranti, A., Tontini, A., Tarzia, G., Mor, M., Trezza, V., Goldberg, S. R., Cuomo, V. y Piomelli, D. (2005). Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proceedings of the National Academy of Sciences, 102(51), 18620–18625. https://doi.org/10.1073/pnas.0509591102
Han, X., DeBold, J. F. y Miczek, K. A. (2017). Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism. Psychopharmacology, 234(18), 2813–2821. https://doi.org/10.1007/s00213-017-4676-8
Hassan, A. M., Mancano, G., Kashofer, K., Fröhlich, E. E., Matak, A., Mayerhofer, R., Reichmann, F., Olivares, M., Neyrinck, A. M., Delzenne, N. M., Claus, S. P. y Holzer, P. (2019). High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome. Nutritional Neuroscience, 22(12), 877–893. https://doi.org/10.1080/1028415X.2018.1465713
Herhaus, B., Ullmann, E., Chrousos, G. y Petrowski, K. (2020). High/low cortisol reactivity and food intake in people with obesity and healthy weight. Translational Psychiatry, 10(1), 40. https://doi.org/10.1038/s41398-020-0729-6
Hill, M. N., Patel, S., Carrier, E. J., Rademacher, D. J., Ormerod, B. K., Hillard, C. J. y Gorzalka, B. B. (2005). Downregulation of Endocannabinoid Signaling in the Hippocampus Following Chronic Unpredictable Stress. Neuropsychopharmacology, 30(3), 508–515. https://doi.org/10.1038/sj.npp.1300601
Hudson, J. I., Hiripi, E., Pope, H. G. y Kessler, R. C. (2007). The Prevalence and Correlates of Eating Disorders in the National Comorbidity Survey Replication. Biological Psychiatry, 61(3), 348–358. https://doi.org/10.1016/j.biopsych.2006.03.040
Hu, W., Zhang, M., Czéh, B., Zhang, W. y Flügge, G. (2011). Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats. Brain Research Bulletin, 85(6), 374–379. https://doi.org/10.1016/j.brainresbull.2011.04.005
Iqbal, A., Hamid, A., Ahmad, S. M. y Lutfy, K. (2023). The Role of Mu Opioid Receptors in High Fat Diet-Induced Reward and Potentiation of the Rewarding Effect of Oxycodone. Life, 13(3), 619. https://doi.org/10.3390/life13030619
Jarosz, P. A., Kessler, J. T., Sekhon, P. y Coscina, D. V. (2007). Conditioned place preferences (CPPs) to high-caloric “snack foods” in rat strains genetically prone vs. resistant to diet-induced obesity: Resistance to naltrexone blockade. Pharmacology Biochemistry and Behavior, 86(4), 699–704. https://doi.org/10.1016/j.pbb.2007.02.017
Kalyani, M., Hasselfeld, K., Janik, J. M., Callahan, P. y Shi, H. (2016). Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice. PLOS ONE, 11(11), e0166416. https://doi.org/10.1371/journal.pone.0166416
Kawahara, Y., Kaneko, F., Yamada, M., Kishikawa, Y., Kawahara, H. y Nishi, A. (2013). Food reward-sensitive interaction of ghrelin and opioid receptor pathways in mesolimbic dopamine system. Neuropharmacology, 67, 395–402. https://doi.org/10.1016/j.neuropharm.2012.11.022
Kim, Y., Yang, H. Y., Kim, A.-J. y Lim, Y. (2013). Academic stress levels were positively associated with sweet food consumption among Korean high-school students. Nutrition, 29(1), 213–218. https://doi.org/10.1016/j.nut.2012.08.005
Koch, J. E. (2001). Δ9-THC stimulates food intake in Lewis rats: effects on chow, high-fat and sweet high-fat diets. Pharmacology Biochemistry and Behavior, 68(3), 539–543. https://doi.org/10.1016/S0091-3057(01)00467-1
Komatsu, H., Ohara, A., Sasaki, K., Abe, H., Hattori, H., Hall, F. S., Uhl, G. R. y Sora, I. (2011). Decreased response to social defeat stress in μ-opioid-receptor knockout mice. Pharmacology Biochemistry and Behavior, 99(4), 676–682. https://doi.org/10.1016/j.pbb.2011.06.008
Konttinen, H. (2020). Emotional eating and obesity in adults: The role of depression, sleep and genes. Proceedings of the Nutrition Society, 79(3), 283–289. https://doi.org/10.1017/S0029665120000166
Koob, G. F. (2009). Brain stress systems in the amygdala and addiction. Brain Research, 1293, 61–75. https://doi.org/10.1016/j.brainres.2009.03.038
Koob, G. F. (2010). The role of CRF and CRF-related peptides in the dark side of addiction. Brain Research, 1314, 3–14. https://doi.org/10.1016/j.brainres.2009.11.008
Koob, G. F. y Volkow, N. D. (2010). Neurocircuitry of Addiction. Neuropsychopharmacology, 35(1), 217–238. https://doi.org/10.1038/npp.2009.110
la Fleur, S. E., Houshyar, H., Roy, M. y Dallman, M. F. (2005). Choice of Lard, But Not Total Lard Calories, Damps Adrenocorticotropin Responses to Restraint. Endocrinology, 146(5), 2193–2199. https://doi.org/10.1210/en.2004-1603
Leigh Gibson, E. (2006). Emotional influences on food choice: Sensory, physiological and psychological pathways. Physiology & Behavior, 89(1), 53–61. https://doi.org/10.1016/j.physbeh.2006.01.024
Linders, L. E., Patrikiou, L., Soiza-Reilly, M., Schut, E. H. S., van Schaffelaar, B. F., Böger, L., Wolterink-Donselaar, I. G., Luijendijk, M. C. M., Adan, R. A. H. y Meye, F. J. (2022). Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food. Nature Communications, 13(1), 6898. https://doi.org/10.1038/s41467-022-34625-7
Li, Y., Chen, H., Wang, J., Wang, J., Niu, X., Wang, C., Qin, D., Li, F., Wang, Y., Xiong, J., Liu, S., Huang, L., Zhang, X., Gao, F., Gao, D., Fan, M., Xiao, X. y Wang, Z.-H. (2022). Inflammation-activated C/EBPβ mediates high-fat diet-induced depression-like behaviors in mice. Frontiers in Molecular Neuroscience, 15. https://doi.org/10.3389/fnmol.2022.1068164
Loebens, M. y Barros, H. M. T. (2003). Diet influences cocaine withdrawal behaviors in the forced swimming test. Pharmacology Biochemistry and Behavior, 74(2), 259–267. https://doi.org/10.1016/S0091-3057(02)00924-3
Logrip, M. L., Zorrilla, E. P. y Koob, G. F. (2012). Stress modulation of drug self-administration: Implications for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology, 62(2), 552–564. https://doi.org/10.1016/j.neuropharm.2011.07.007
MacKay, J. C., Kent, P., James, J. S., Cayer, C. y Merali, Z. (2017). Ability of palatable food consumption to buffer against the short- and long-term behavioral consequences of social defeat exposure during juvenility in rats. Physiology & Behavior, 177, 113–121. https://doi.org/10.1016/j.physbeh.2017.04.002
Mahdavi, K., Zendehdel, M. y Baghbanzadeh, A. (2023). Central effects of opioidergic system on food intake in birds and mammals: A review. Veterinary Research Communications, 47(3), 1103–1114. https://doi.org/10.1007/S11259-023-10142-W
Maldonado, C., Rodríguez-Arias, M., Castillo, A., Aguilar, M. A. y Miñarro, J. (2006). Gamma-hydroxybutyric acid affects the acquisition and reinstatement of cocaine-induced conditioned place preference in mice. Behavioural Pharmacology, 17(2), 119–131. https://doi.org/10.1097/01.fbp.0000190685.84984.ec
Maniam, J. y Morris, M. J. (2010). Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: Role of hippocampus. Psychoneuroendocrinology, 35(10), 1553–1564. https://doi.org/10.1016/j.psyneuen.2010.05.012
Martire, S. I., Maniam, J., South, T., Holmes, N., Westbrook, R. F. y Morris, M. J. (2014). Extended exposure to a palatable cafeteria diet alters gene expression in brain regions implicated in reward, and withdrawal from this diet alters gene expression in brain regions associated with stress. Behavioural Brain Research, 265, 132–141. https://doi.org/10.1016/j.bbr.2014.02.027
Miczek, K., Yap, J. y Covingtoniii, H. (2008). Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake. Pharmacology & Therapeutics, 120(2), 102–128. https://doi.org/10.1016/j.pharmthera.2008.07.006
Mizoguchi, A., Banno, R., Sun, R., Yaginuma, H., Taki, K., Kobayashi, T., Sugiyama, M., Tsunekawa, T., Onoue, T., Takagi, H., Hagiwara, D., Ito, Y., Iwama, S., Suga, H., Nagai, T., Yamada, K. y Arima, H. (2021). Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice. Scientific Reports, 11(1), 12873. https://doi.org/10.1038/s41598-021-92386-7
Montagud-Romero, S., Aguilar, M. A., Maldonado, C., Manzanedo, C., Miñarro, J. y Rodríguez-Arias, M. (2015). Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice. Pharmacology Biochemistry and Behavior, 135, 1–12. https://doi.org/10.1016/j.pbb.2015.05.008
Montagud-Romero, S., Reguilón, M. D., Pascual, M., Blanco-Gandía, M. C., Guerri, C., Miñarro, J. y Rodríguez-Arias, M. (2021). Critical role of TLR4 in uncovering the increased rewarding effects of cocaine and ethanol induced by social defeat in male mice. Neuropharmacology, 182, 108368. https://doi.org/10.1016/j.neuropharm.2020.108368
Montagud-Romero, S., Reguilon, M. D., Roger-Sanchez, C., Pascual, M., Aguilar, M. A., Guerri, C., Miñarro, J. y Rodríguez-Arias, M. (2016). Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 71, 144–154. https://doi.org/10.1016/j.pnpbp.2016.07.008
Morales, L., Del Olmo, N., Valladolid-Acebes, I., Fole, A., Cano, V., Merino, B., Stucchi, P., Ruggieri, D., López, L., Alguacil, L. F. y Ruiz-Gayo, M. (2012). Shift of Circadian Feeding Pattern by High-Fat Diets Is Coincident with Reward Deficits in Obese Mice. PLOS ONE, 7(5), e36139. https://doi.org/10.1371/journal.pone.0036139
Neisewander, J. L., Peartree, N. A. y Pentkowski, N. S. (2012). Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction. Psychopharmacology, 224(1), 33–56. https://doi.org/10.1007/s00213-012-2853-3
Ong, Z. Y., Wanasuria, A. F., Lin, M. Z. P., Hiscock, J. y Muhlhausler, B. S. (2013). Chronic intake of a cafeteria diet and subsequent abstinence. Sex-specific effects on gene expression in the mesolimbic reward system. Appetite, 65, 189–199. https://doi.org/10.1016/j.appet.2013.01.014
Otsuka, A., Shiuchi, T., Chikahisa, S., Shimizu, N. y Séi, H. (2019). Sufficient intake of high-fat food attenuates stress-induced social avoidance behavior. Life Sciences, 219, 219–230. https://doi.org/10.1016/j.lfs.2019.01.012
Packard, A. E. B., Ghosal, S., Herman, J. P., Woods, S. C. y Ulrich-Lai, Y. M. (2014). Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes. Psychoneuroendocrinology, 47, 178–188. https://doi.org/10.1016/j.psyneuen.2014.05.016
Parylak, S. L., Cottone, P., Sabino, V., Rice, K. C. y Zorrilla, E. P. (2012). Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: Lack of withdrawal-like responses. Physiology & Behavior, 107(2), 231–242. https://doi.org/10.1016/j.physbeh.2012.06.017
Pecoraro, N., Reyes, F., Gomez, F., Bhargava, A. y Dallman, M. F. (2004). Chronic Stress Promotes Palatable Feeding, which Reduces Signs of Stress: Feedforward and Feedback Effects of Chronic Stress. Endocrinology, 145(8), 3754–3762. https://doi.org/10.1210/en.2004-0305
Peleg-Raibstein, D., Sarker, G., Litwan, K., Krämer, S. D., Ametamey, S. M., Schibli, R. y Wolfrum, C. (2016). Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition. Translational Psychiatry, 6(10), e911–e911. https://doi.org/10.1038/tp.2016.176
Pitman, K. A. y Borgland, S. L. (2015). Changes in mu-opioid receptor expression and function in the mesolimbic system after long-term access to a palatable diet. Pharmacology & Therapeutics, 154, 110–119. https://doi.org/10.1016/j.pharmthera.2015.07.005
Puhl, M. D., Cason, A. M., Wojnicki, F. H. E., Corwin, R. L. y Grigson, P. S. (2011). A history of bingeing on fat enhances cocaine seeking and taking. Behavioral Neuroscience, 125(6), 930–942. https://doi.org/10.1037/a0025759
Rademacher, D. J. y Hillard, C. J. (2007). Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 31(3), 633–641. https://doi.org/10.1016/j.pnpbp.2006.12.013
Reguilón, M. D., Ferrer-Pérez, C., Ballestín, R., Miñarro, J. y Rodríguez-Arias, M. (2020). Voluntary wheel running protects against the increase in ethanol consumption induced by social stress in mice. Drug and Alcohol Dependence, 212, 108004. https://doi.org/10.1016/j.drugalcdep.2020.108004
Reguilón, M. D., Ferrer-Pérez, C., Miñarro, J. y Rodríguez-Arias, M. (2021). Oxytocin reverses ethanol consumption and neuroinflammation induced by social defeat in male mice. Hormones and Behavior, 127, 104875. https://doi.org/10.1016/j.yhbeh.2020.104875
Reguilón, M. D., Montagud-Romero, S., Ferrer-Pérez, C., Roger-Sánchez, C., Aguilar, M. A., Miñarro, J. y Rodríguez-Arias, M. (2017). Dopamine D2 receptors mediate the increase in reinstatement of the conditioned rewarding effects of cocaine induced by acute social defeat. European Journal of Pharmacology, 799, 48–57. https://doi.org/10.1016/j.ejphar.2017.01.039
Reich, C. G., Taylor, M. E. y McCarthy, M. M. (2009). Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behavioural Brain Research, 203(2), 264–269. https://doi.org/10.1016/j.bbr.2009.05.013
Ródenas-González, F., Blanco-Gandía, M. del C., Pascual, M., Molari, I., Guerri, C., López, J. M. y Rodríguez-Arias, M. (2021). A limited and intermittent access to a high-fat diet modulates the effects of cocaine-induced reinstatement in the conditioned place preference in male and female mice. Psychopharmacology, 238(8), 2091–2103. https://doi.org/10.1007/s00213-021-05834-7
Rodríguez-Arias, M., Montagud-Romero, S., Guardia Carrión, A. M., Ferrer-Pérez, C., Pérez-Villalba, A., Marco, E., López Gallardo, M., Viveros, M.-P. y Miñarro, J. (2018). Social stress during adolescence activates long-term microglia inflammation insult in reward processing nuclei. PLOS ONE, 13(10), e0206421. https://doi.org/10.1371/journal.pone.0206421
Rodríguez‐Arias, M., Montagud‐Romero, S., Rubio‐Araiz, A., Aguilar, M. A., Martín‐García, E., Cabrera, R., Maldonado, R., Porcu, F., Colado, M. I. y Miñarro, J. (2017). Effects of repeated social defeat on adolescent mice on cocaine‐induced CPP and self‐administration in adulthood: Integrity of the blood–brain barrier. Addiction Biology, 22(1), 129–141. https://doi.org/10.1111/adb.12301
Rossi, S., De Chiara, V., Musella, A., Kusayanagi, H., Mataluni, G., Bernardi, G., Usiello, A. y Centonze, D. (2008). Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum. The Journal of Neuroscience, 28(29), 7284–7292. https://doi.org/10.1523/JNEUROSCI.5346-07.2008
Sakamoto, K., Matsumura, S., Okafuji, Y., Eguchi, A., Yoneda, T., Mizushige, T., Tsuzuki, S., Inoue, K. y Fushiki, T. (2015). The opioid system contributes to the acquisition of reinforcement for dietary fat but is not required for its maintenance. Physiology & Behavior, 138, 227–235. https://doi.org/10.1016/j.physbeh.2014.11.001
Shimamoto, A. (2018). Social Defeat Stress, Sex, and Addiction-Like Behaviors. In International Review of Neurobiology (Vol. 140, pp. 271–313). Elsevier. https://doi.org/10.1016/bs.irn.2018.07.009
Shimizu, T., Ishida, A., Hagiwara, M., Ueda, Y., Hattori, A., Tajiri, N. y Hida, H. (2020). Social Defeat Stress in Adolescent Mice Induces Depressive-like Behaviors with Reduced Oligodendrogenesis. Neuroscience, 443, 218–232. https://doi.org/10.1016/j.neuroscience.2020.07.002
Sinha, R. y Jastreboff, A. M. (2013). Stress as a Common Risk Factor for Obesity and Addiction. Biological Psychiatry, 73(9), 827–835. https://doi.org/10.1016/j.biopsych.2013.01.032
Smith, S. L., Harrold, J. A. y Williams, G. (2002). Diet-induced obesity increases μ opioid receptor binding in specific regions of the rat brain. Brain Research, 953(1–2), 215–222. https://doi.org/10.1016/S0006-8993(02)03291-2
Soto, M., Chaumontet, C., Even, P. C., Nadkarni, N., Piedcoq, J., Darcel, N., Tomé, D. y Fromentin, G. (2015). Intermittent access to liquid sucrose differentially modulates energy intake and related central pathways in control or high-fat fed mice. Physiology & Behavior, 140, 44–53. https://doi.org/10.1016/j.physbeh.2014.12.008
Spear, L. P. (2000). Neurobehavioral Changes in Adolescence. Current Directions in Psychological Science, 9(4), 111–114. https://doi.org/10.1111/1467-8721.00072
Steinberg, L. (2010). A dual systems model of adolescent risk‐taking. Developmental Psychobiology, 52(3), 216–224. https://doi.org/10.1002/dev.20445
Steiner, M. A., Wanisch, K., Monory, K., Marsicano, G., Borroni, E., Bächli, H., Holsboer, F., Lutz, B. y Wotjak, C. T. (2008). Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice. The Pharmacogenomics Journal, 8(3), 196–208. https://doi.org/10.1038/sj.tpj.6500466
Tsai, S.-F., Hsu, P.-L., Chen, Y.-W., Hossain, M. S., Chen, P.-C., Tzeng, S.-F., Chen, P.-S. y Kuo, Y.-M. (2022). High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens. Molecular Psychiatry, 27(11), 4372–4384. https://doi.org/10.1038/s41380-022-01787-1
Ulrich-Lai, Y. M., Ostrander, M. M. y Herman, J. P. (2011). HPA axis dampening by limited sucrose intake: Reward frequency vs. caloric consumption. Physiology & Behavior, 103(1), 104–110. https://doi.org/10.1016/j.physbeh.2010.12.011
Ulug, E., Acikgoz Pinar, A. y Yildiz, B. O. (2025). Impact of ultra-processed foods on hedonic and homeostatic appetite regulation: A systematic review. Appetite, 213. https://doi.org/10.1016/j.appet.2025.108139
Valverde, O. y Torrens, M. (2012). CB1 receptor-deficient mice as a model for depression. Neuroscience, 204, 193–206. https://doi.org/10.1016/j.neuroscience.2011.09.031
Vidal-Infer, A., Arenas, M. C., Daza-Losada, M., Aguilar, M. A., Miñarro, J. y Rodríguez-Arias, M. (2012). High novelty-seeking predicts greater sensitivity to the conditioned rewarding effects of cocaine. Pharmacology Biochemistry and Behavior, 102(1), 124–132. https://doi.org/10.1016/j.pbb.2012.03.031
Volkow, N. D. y Blanco, C. (2023). Substance use disorders: A comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention. World Psychiatry, 22(2), 203–229. https://doi.org/10.1002/wps.21073
Volkow, N. D., Wang, G. ‐J., Tomasi, D. y Baler, R. D. (2013). Obesity and addiction: Neurobiological overlaps. Obesity Reviews, 14(1), 2–18. https://doi.org/10.1111/j.1467-789X.2012.01031.x
Vucetic, Z., Kimmel, J. y Reyes, T. M. (2011). Chronic High-Fat Diet Drives Postnatal Epigenetic Regulation of μ-Opioid Receptor in the Brain. Neuropsychopharmacology, 36(6), 1199–1206. https://doi.org/10.1038/npp.2011.4
Wang, W., Liu, W., Duan, D., Bai, H., Wang, Z. y Xing, Y. (2021). Chronic social defeat stress mouse model: Current view on its behavioral deficits and modifications. Behavioral Neuroscience, 135(3), 326–335. https://doi.org/10.1037/bne0000418
Wang, W., Sun, D., Pan, B., Roberts, C. J., Sun, X., Hillard, C. J. y Liu, Q. (2010). Deficiency in Endocannabinoid Signaling in the Nucleus Accumbens Induced by Chronic Unpredictable Stress. Neuropsychopharmacology, 35(11), 2249–2261. https://doi.org/10.1038/npp.2010.99
Weathington, J. M. y Cooke, B. M. (2012). Corticotropin-Releasing Factor Receptor Binding in the Amygdala Changes Across Puberty in a Sex-Specific Manner. Endocrinology, 153(12), 5701–5705. https://doi.org/10.1210/en.2012-1815
Zeeni, N., Daher, C., Fromentin, G., Tome, D., Darcel, N. y Chaumontet, C. (2013). A cafeteria diet modifies the response to chronic variable stress in rats. Stress, 16(2), 211–219. https://doi.org/10.3109/10253890.2012.708952
Zellner, D. A., Loaiza, S., Gonzalez, Z., Pita, J., Morales, J., Pecora, D. y Wolf, A. (2006). Food selection changes under stress. Physiology & Behavior, 87(4), 789–793. https://doi.org/10.1016/j.physbeh.2006.01.014
