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1.
Appetite ; 200: 107504, 2024 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-38768926

RESUMEN

The dynorphin peptides are the endogenous ligands for the kappa opioid receptor (KOR) and regulate food intake. Administration of dynorphin-A1-13 (DYN) in the paraventricular hypothalamic nucleus (PVN) increases palatable food intake, and this effect is blocked by co-administration of the orexin-A neuropeptide, which is co-released with DYN in PVN from neurons located in the lateral hypothalamus. While PVN administration of DYN increases palatable food intake, whether it increases food-seeking behaviors has yet to be examined. We tested the effects of DYN and norBNI (a KOR antagonist) on the seeking and consumption of sucrose using a progressive ratio (PR) and demand curve (DC) tasks. In PVN, DYN did not alter the sucrose breaking point (BP) in the PR task nor the elasticity or intensity of demand for sucrose in the DC task. Still, DYN reduced the delay in obtaining sucrose and increased licks during sucrose intake in the PR task, irrespective of the co-administration of orexin-A. In PVN, norBNI increased the delay in obtaining sucrose and reduced licks during sucrose intake in the PR task while increasing elasticity without altering intensity of demand in the DC task. However, subcutaneous norBNI reduced the BP for sucrose and increased the delay in obtaining sucrose in the PR task while reducing the elasticity of demand. Together, these data show different effects of systemic and PVN blockade of KOR on food-seeking, consummatory behaviors, and incentive motivation for sucrose and suggest that KOR activity in PVN is necessary but not sufficient to drive seeking behaviors for palatable food.


Asunto(s)
Dinorfinas , Motivación , Núcleo Hipotalámico Paraventricular , Receptores Opioides kappa , Receptores Opioides kappa/metabolismo , Dinorfinas/farmacología , Dinorfinas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Animales , Masculino , Motivación/efectos de los fármacos , Orexinas , Ratas , Ratas Sprague-Dawley , Naltrexona/farmacología , Naltrexona/análogos & derivados , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Sacarosa , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/psicología , Antagonistas de Narcóticos/farmacología
2.
Neurosci Biobehav Rev ; 152: 105288, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37331611

RESUMEN

The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.


Asunto(s)
Motivación , Receptores Opioides , Analgésicos Opioides/farmacología , Ingestión de Alimentos , Conducta Alimentaria , Ligandos , Receptores Opioides mu
3.
Nutr Neurosci ; 25(5): 1105-1114, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33151127

RESUMEN

The orexin peptides promote hedonic intake and other reward behaviors through different brain sites. The opioid dynorphin peptides are co-released with orexin peptides but block their effects on reward in the ventral tegmental area (VTA). We previously showed that in the paraventricular hypothalamic nucleus (PVN), dynorphin and not orexin peptides enhance hedonic intake, suggesting they have brain-site-specific effects. Obesity alters the expression of orexin and dynorphin receptors, but whether their expression across different brain sites is important to hedonic intake is unclear. We hypothesized that hedonic intake is regulated by orexin and dynorphin peptides in PVN and that hedonic intake in obesity correlates with expression of their receptors. Here we show that in mice, injection of DYN-A1-13 (an opioid dynorphin peptide) in the PVN enhanced hedonic intake, whereas in the VTA, injection of OXA (orexin-A, an orexin peptide) enhanced hedonic intake. In PVN, OXA blunted the increase in hedonic intake caused by DYN-A1-13. In PVN, injection of norBNI (opioid receptor antagonist) reduced hedonic intake but a subsequent OXA injection failed to increase hedonic intake, suggesting that OXA activity in PVN is not influenced by endogenous opioid activity. In the PVN, DYN-A1-13 increased the intake of the less-preferred food in a two-food choice task. In obese mice fed a cafeteria diet, orexin 1 receptor mRNA across brain sites involved in hedonic intake correlated with fat preference but not caloric intake. Together, these data support that orexin and dynorphin peptides regulate hedonic intake in an opposing manner with brain-site-specific effects.


Asunto(s)
Dinorfinas , Núcleo Hipotalámico Paraventricular , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacología , Animales , Encéfalo/metabolismo , Dinorfinas/metabolismo , Dinorfinas/farmacología , Ratones , Obesidad/metabolismo , Orexinas/metabolismo
4.
Neuroscience ; 371: 337-345, 2018 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-29203229

RESUMEN

The dynorphin (DYN) peptide family includes opioid and non-opioid peptides, yet the physiological role of the non-opioid DYN peptides remains poorly understood. Recent evidence shows that administering the non-opioid peptide DYN-A2-17 into the paraventricular hypothalamic nucleus (PVN) simultaneously increased short-term intake of standard rodent chow and spontaneous physical activity (SPA). The present studies aimed to expand upon the mechanisms and role of DYN-A2-17 on food intake and energy expenditure. Injection of DYN-A2-17 in PVN increased SPA, energy expenditure and wheel running in the absence of food. Repeated DYN-A2-17 injection in PVN increased short-term chow intake, but this effect habituated over time and failed to alter cumulative food intake, body weight or adiposity. Pre-treatment with a CRF receptor antagonist into PVN blocked the effects of DYN-A2-17 on food intake while injection of DYN-A2-17 in PVN increased plasma ACTH. Finally, as DYN peptides are co-released with orexin peptides, we compared the effects of DYN-A2-17 to orexin-A and the opioid peptide DYN-A1-13 on food choice and intake in PVN when palatable snacks and chow were available. DYN-A1-13 selectively increased intake of palatable snacks. DYN-A2-17 and orexin-A decreased palatable snack intake while orexin-A also increased chow intake. These findings demonstrate that the non-opioid peptide DYN-A2-17 acutely regulates physical activity, energy expenditure and food intake without long-term effects on energy balance. These data also propose different roles of opioid, non-opioid DYN and orexin peptides on food choice and intake when palatable and non-palatable food options are available.


Asunto(s)
Fármacos del Sistema Nervioso Central/farmacología , Dinorfinas/farmacología , Metabolismo Energético/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Carrera , Adiposidad/efectos de los fármacos , Adiposidad/fisiología , Hormona Adrenocorticotrópica/sangre , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Metabolismo Energético/fisiología , Conducta Alimentaria/fisiología , Masculino , Ratones Endogámicos BALB C , Orexinas/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Carrera/fisiología
5.
Peptides ; 76: 14-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26654796

RESUMEN

Food intake and physical activity are regulated by multiple neuropeptides, including orexin and dynorphin (DYN). Orexin-A (OXA) is one of two orexin peptides with robust roles in regulation of food intake and spontaneous physical activity (SPA). DYN collectively refers to several peptides, some of which act through opioid receptors (opioid DYN) and some whose biological effects are not mediated by opioid receptors (non-opioid DYN). While opioid DYN is known to increase food intake, the effects of non-opioid DYN peptides on food intake and SPA are unknown. Neurons that co-express and release OXA and DYN are located within the lateral hypothalamus. Limited evidence suggests that OXA and opioid DYN peptides can interact to modulate some aspects of behaviors classically related to orexin peptide function. The paraventricular hypothalamic nucleus (PVN) is a brain area where OXA and DYN peptides might interact to modulate food intake and SPA. We demonstrate that injection of des-Tyr-dynorphin (DYN-A(2-17), a non opioid DYN peptide) into the PVN increases food intake and SPA in adult mice. Co-injection of DYN-A(2-17) and OXA in the PVN further increases food intake compared to DYN-A(2-17) or OXA alone. This is the first report describing the effects of non-opioid DYN-A(2-17) on food intake and SPA, and suggests that DYN-A(2-17) interacts with OXA in the PVN to modulate food intake. Our data suggest a novel function for non-opioid DYN-A(2-17) on food intake, supporting the concept that some behavioral effects of the orexin neurons result from combined actions of the orexin and DYN peptides.


Asunto(s)
Dinorfinas/fisiología , Orexinas/metabolismo , Fragmentos de Péptidos/fisiología , Animales , Regulación del Apetito , Ingestión de Energía , Masculino , Ratones Endogámicos BALB C , Actividad Motora
6.
Physiol Behav ; 152(Pt A): 315-22, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26440318

RESUMEN

Despite the increase in obesity prevalence over the last decades, humans show large inter-individual variability for susceptibility to diet-induced obesity. Understanding the biological basis of this susceptibility could identify new therapeutic alternatives against obesity. We characterized behavioral changes associated with propensity to obesity induced by cafeteria (CAF) diet consumption in mice. We show that Balb/c mice fed a CAF diet display a large inter-individual variability in susceptibility to diet-induced obesity, such that based on changes in adiposity we can classify mice as obesity prone (OP) or obesity resistant (OR). Both OP and OR were hyperphagic relative to control-fed mice but caloric intake was similar between OP and OR mice. In contrast, OR had a larger increase in locomotor activity following CAF diet compared to OP mice. Obesity resistant and prone mice showed similar intake of sweet snacks, but OR ate more savory snacks than OP mice. Two bottle sucrose preference tests showed that OP decreased their sucrose preference compared to OR mice after CAF diet feeding. Finally, to test the robustness of the OR phenotype in response to further increases in caloric intake, we fed OR mice with a personalized CAF (CAF-P) diet based on individual snack preferences. When fed a CAF-P diet, OR increased their calorie intake compared to OP mice fed the standard CAF diet, but did not reach adiposity levels observed in OP mice. Together, our data show the contribution of hedonic intake, individual snack preference and physical activity to individual susceptibility to obesity in Balb/c mice fed a standard and personalized cafeteria-style diet.


Asunto(s)
Dieta , Conducta Alimentaria/fisiología , Preferencias Alimentarias/fisiología , Ratones Endogámicos BALB C/fisiología , Ratones Obesos/fisiología , Actividad Motora/fisiología , Alimentación Animal/efectos adversos , Animales , Conducta de Elección/fisiología , Dieta/efectos adversos , Dieta/psicología , Sacarosa en la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Conducta Alimentaria/psicología , Preferencias Alimentarias/psicología , Predisposición Genética a la Enfermedad , Hiperfagia/etiología , Hiperfagia/fisiopatología , Hiperfagia/psicología , Masculino , Ratones Endogámicos BALB C/genética , Ratones Endogámicos BALB C/psicología , Ratones Obesos/genética , Ratones Obesos/psicología , Especificidad de la Especie
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