Exploratory study of the prevalence of food addiction and its relationship with executive functioning, depression, and reinforcement sensitivity in a sample of Mexican adults.

Introduction: The study of food addiction (FA) has become relevant due to its high prevalence, the negative impact on quality of life, and its association with neuropsychological and psychiatric symptoms. Several studies have provided scientific support for these associations, however, the results are contradictory. Additionally, studies have unsuccessfully elucidated the true nature of the failures in executive functioning in people with FA symptomatology, particularly when it comes to executive deficits. Therefore, the purpose of this research was to establish whether the presence of executive dysfunction, depressive symptoms and binge eating problems, as well as high reward sensitivity entails a greater severity in FA traits and high body mass index (BMI) in a sample of Mexican adults. Methods: The sample consisted of Mexican men and women between 21-59 years (n = 36); who completed self-report questionnaires and performance tests to measure the study variables. Additionally, BMI was estimated with self-reported height and weight. Results: Our results showed that a high number of FA symptoms were associated with higher executive dysfunction scores, greater reward sensitivity, and more severe depressive and binge eating problems. Furthermore, factors that are more strongly associated with higher scores of FA include severe executive deficits, greater activation of the punishment avoidance system, and persistence in the search for reward when the depressive symptoms increased. The factors that best explained changes in the estimated BMI of women were a decreased crystallized intellectual capacity and the inability to control food intake as the number of FA symptoms increased. Discussion: In summary, the cognitive functioning profile characterized by general failure of the executive functioning, as well as a greater activation of the Punishment Avoidance System and persistence in the search for reward, were associated with greater severity of FA symptoms, especially when the depressive symptomatology was severe. In parallel, the psychopathology in participants associated with FA confirms the contribution of anxious and depressive symptomatology and borderline personality traits which could facilitate the expression of clinically relevant FA symptoms in women. Finally, we found that decreased crystallized intellectual capacity and inability to control food intake were linked to higher BMI when the number of FA symptoms increased.

El consumo de bebidas dulces incrementa diferencialmente la expresión de Oxitocina en núcleos hipotalámicos / The consumption of sweet drinks differentially increases the expression of oxytocin in hypothalamic nuclei

Resumen Se reconoce la participación de la oxitocina en el control de la alimentación, pero su mecanismo de acción no se ha establecido totalmente. Por tanto, el objetivo de esta investigación fue evaluar el efecto del acceso intermitente a una solución de sacarosa, sobre la expresión de las neuronas del núcleo paraventricular (PVN) y del núcleo supraótico (SON) que producen oxitocina (Oxt), y caracterizar la microestructura de la conducta de beber en ratas saciadas. Se tuvieron tres grupos de ratas macho Wistar saciadas, y en la primera hora al inicio del periodo de luz, el grupo Control tuvo agua, el grupo Restringido 5g de una solución de sacarosa al 20% y el grupo Ad libitum acceso libre a la solución de sacarosa. Los sujetos incrementaron el consumo de la solución de sacarosa a pesar de estar saciados; debido a la interrupción del estado de saciedad y la demora de la satisfacción. La actividad de las neuronas de Oxt se incrementó en ambos núcleos, en el grupo Restringido la mayor expresión se observó en el SON y en el grupo Ad libitum en el PVN. No se encontró correlación entre la cantidad de bebida ingerida y la actividad de las neuronas Oxt.

Abstract The role of oxytocin in feeding control is recognized, but its mechanism of action has not been fully established. Therefore, the aim of this research was to evaluate the effect of intermittent access to a sucrose solution on the expression of paraventricular nucleus (PVN) and supraotic nucleus (SON) neurons that produce oxytocin (Oxt), and to characterize the microstructure of drinking behavior in satiated rats. Three groups of male Wistar rats satiated were used, and in the first hour at the beginning of the light period, a Control group had water, a Restricted group 5g of a 20% sucrose solution and Ad libitum group with free access to sucrose solution. The experimental subjects increased the consumption of the sucrose solution despite being satiated, due to the interruption of the state of satiety and the delay of the satiation process. Oxt neurons increased their activity in both nuclei, in the Restricted group the highest expression was observed in the SON and in the Ad libitum group in the PVN. No correlation was found between the amount of drink ingested and the activity of Oxt neurons.

Stimulation of melanocortin-3 receptors accelerates the satiation process and increases the α-MSH expression in high-fat diet-fed rats.

The knowledge about the role of MC3 receptors (MC3r) in the regulation of feeding behavior is limited. The present study was conducted to determine whether MC3r mediates the hypophagic effects of the melanocortins under conditions of positive energy balance. Male Wistar rats were fed with a high-fat diet (HFD) for 15 days and on day 16 the animals received an intracerebroventricular injection of the following treatments: Vehicle, D-Trp8-γ-melanocyte-stimulating hormone (MSH; MC3r agonist), SHU9119 (MC3r/MC4r antagonist), or D-Trp8-γ-MSH+SHU9119. Food intake was measured and the behavioral satiety sequence (BSS) analysis was carried out during the first hour of the dark phase. The c-Fos and α-MSH immunoreactivity in the arcuate nucleus (ARC) was evaluated 60 min later the onset of food intake. The results indicated that D-Trp8-γ-MSH decreased the ingestion of the HFD and this effect is associated with the early development of the satiation process Moreover, the D-Trp8-γ-MSH increased the accumulation of the α-MSH in the ARC and the c-Fos activity in the PVN. The antagonist SHU9119 partially prevented the D-Trp8-γ-MSH-induced hypophagia. Moreover, behavioral analysis suggests that central activation of MC3r accelerated the cessation of feeding in conditions of positive energy balance; the possible role of MC4r is discussed. Present data indicate that central stimulation of MC3r prevented the overconsumption of the HFD without affecting the natural satiation process, suggesting a potential use of MC3r for the treatment of eating disorders that are stimulated by hypercaloric diets. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CB1/5-HT/GABA interactions and food intake regulation.

Despite historically the serotonergic, GABAergic, and cannabinoid systems have been shown to play a crucial role in the central regulation of eating behavior, interest in the study of the interactions of these neurotransmission systems has only now been investigated. Current evidence suggests that serotonin may influence normal and pathological eating behavior in significantly more complex ways than was initially thought. This knowledge has opened the possibility of exploring the potential clinical utility of new therapeutic strategies more effective and safer than the current approaches to treat pathological eating behavior. Furthermore, the nature and complexity of the interactions between these neurotransmitter systems have provided a better understanding of the pathophysiological mechanisms not only of eating behavior and eating disorders but also of some of the comorbidities associated with modulation of cortical circuits, which are involved in high order cognitive processes. Accordingly, in the present chapter, the clinical and experimental findings of the interactions between serotonin, GABA, and cannabinoids are synthesized, emphasizing the pharmacological, neurophysiological, and neuroanatomical aspects that could potentially improve the current therapeutic approaches against pathological eating behavior.

Melanocortinas y su participación en el desarrollo de la obesidad

Resumen La obesidad y el sobrepeso son problemas de origen multifactorial, la interacción de los factores ambientales, genéticos y conductuales parecen ser la clave en el desarrollo de esta patología. Los receptores MC3 (rMC3) y MC4 (rMC4), participan en la regulación del balance energético (consumo de alimento, gasto energético y peso corporal), su mutación genética está asociada con el incremento de la adiposidad y el desarrollo de la obesidad. El conocimiento que se tiene de estos receptores y su función aún es limitado, principalmente con respecto a los rMC3 y, aunque los rMC4 se están posicionando como un blanco terapéutico potencial para el tratamiento de la obesidad, se requiere de mayor investigación clínica. Por lo tanto, el propósito de este documento es presentar evidencia de la participación de los receptores MC3 y MC4 en el desarrollo de la obesidad, a través de los resultados encontrados en algunas investigaciones, tanto en modelos animales como en humanos.

Abstract Obesity and overweight are problems of multifactorial origin, the interaction of environmental, genetic, and behavioral factors seems to be the key in the development of this pathology. The MC3 (rMC3) and MC4 (rMC4) receptors participate in the regulation of energy balance (food intake, energy expenditure and body weight), their genetic mutation is associated with increased adiposity and the development of obesity. Knowledge of these receptors and their function is still limited, mainly with respect to rMC3 and, although rMC4 are positioning themselves as a potential therapeutic target for the treatment of obesity, further clinical research is required. Therefore, the purpose of this document is to present the participation of MC3 and MC4 receptors in the development of obesity, through the results found in some investigations, both in animal and in human´s models.

Blockade of Intranigral and Systemic D3 Receptors Stimulates Motor Activity in the Rat Promoting a Reciprocal Interaction among Glutamate, Dopamine, and GABA.

In vivo activation of dopamine D3 receptors (D3Rs) depresses motor activity. D3Rs are widely expressed in subthalamic, striatal, and dendritic dopaminergic inputs into the substantia nigra pars reticulata (SNr). In vitro studies showed that nigral D3Rs modulate their neurotransmitter release; thus, it could be that these changes in neurotransmitter levels modify the discharge of nigro-thalamic neurons and, therefore, motor behavior. To determine how the in vitro responses correspond to the in vivo responses, we examined the effect of intra-nigral and systemic blockade of D3Rs in the interstitial content of glutamate, dopamine, and GABA within the SNr using microdialysis coupled to motor activity determinations in freely moving rats. Intranigral unilateral blockade of D3R with GR 103,691 increased glutamate, dopamine, and GABA. Increments correlated with increased ambulatory distance, non-ambulatory activity, and induced contralateral turning. Concomitant blockade of D3R with D1R by perfusion of SCH 23390 reduced the increase of glutamate; prevented the increment of GABA, but not of dopamine; and abolished behavioral effects. Glutamate stimulates dopamine release by NMDA receptors, while blockade with kynurenic acid prevented the increase in dopamine and, in turn, of GABA and glutamate. Finally, systemic administration of D3R selective antagonist U 99194A increased glutamate, dopamine, and GABA in SNr and stimulated motor activity. Blockade of intra-nigral D1R with SCH 23390 prior to systemic U 99194A diminished increases in neurotransmitter levels and locomotor activity. These data highlight the pivotal role of presynaptic nigral D3 and D1R in the control of motor activity and help to explain part of the effects of the in vivo administration of D3R agents.

CB1 receptors in the paraventricular nucleus of the hypothalamus modulate the release of 5-HT and GABA to stimulate food intake in rats.

Endocannabinoids and their receptors not only contribute to the control of natural processes of appetite regulation and energy balance but also have an important role in the pathogenesis of obesity. CB1 receptors (CB1R) are expressed in several hypothalamic nuclei, including the paraventricular nucleus (PVN), where induce potent orexigenic responses. Activation of CB1R in the PVN induces hyperphagia by modulating directly or indirectly orexigenic and anorexigenic signals; however, interaction among these mediators has not been clearly defined. CB1R mRNA is expressed in serotonergic neurons that innervate the PVN, and activation of 5-HT receptors in the PVN constitutes an important satiety signal. Some GABAergic terminals are negatively influenced by 5-HT, suggesting that the hyperphagic effect of CB1R activation could involve changes in serotonergic and GABAergic signaling in the PVN. Accordingly, the present study was aimed to characterize the neurochemical mechanisms related to the hyperphagic effects induced by activation of CB1R in the PVN, studying in vitro and in vivo changes induced by direct activation these receptors. Here, we have found that the neurochemical mechanisms activated by stimulation of CB1 receptors in the PVN involve inhibition of 5-HT release, resulting in a decrease of serotonergic activity mediated by 5-HT1A and 5-HT1B receptors and inducing disinhibition of GABA release to stimulate food intake. In conclusion, these neurochemical changes in the PVN are determinant to the cannabinoid-induced stimulation of food intake. Our findings provide evidence of a functional connection among CB1R and serotonergic and GABAergic systems on the control of appetite regulation mediated by endocannabinoids.

Effects of a high-fat diet on behavioral eating patterns / Efeitos de uma dieta com alto conteúdo de gordura sobre padrões comportamentais alimentares / Efectos de una dieta con alto contenido de grasas sobre patrones conductuales alimentarios

Abstract Excessive consumption of high-fat food has been associated with increased prevalence of obesity. The physiological and metabolic effects of high-fat diets have been extensively studied. Nevertheless, the behavioral mechanisms associated with the development of obesity induced by consumption of these diets has been less explored. Therefore, the aim of the present study was to characterize the changes in the behavioral feeding patterns produced by the consumption of a high-fat diet during 10 days. Male Wistar rats with free access to food were assigned to one of two groups, and for 10 days, they had access to a high-fat diet (45 % calories from fat) or to a standard diet. Detailed analysis of feeding behavior was performed on days 1, 5 and 10 at the beginning of the dark period. The results showed that subjects exposed to the high-fat diet accumulated more body fat and showed increased feeding efficiency, in absence of excessive body weight increase or alterations in the behavioral satiety sequence pattern. These findings suggest that exposure to high-fat diets may produce behavioral changes before excessive gain of body weight occurs, primarily affecting control mechanisms of feeding efficiency.

Resumo O consumo excessivo de alimentos com alto conteúdo de gordura tem sido associado com o aumento da obesidade. Os efeitos fisiológicos e metabólicos do consumo de dietas altas em gordura têm sido estudados extensamente, contudo os mecanismos comportamentais relacionados com o desenvolvimento da obesidade pelo consumo dessas dietas têm-se explorado em menor medida. Portanto, o objetivo deste estudo foi caracterizar as mudanças nos padrões comportamentais da alimentação produzidas pelo consumo de uma dieta alta em gordura durante dez dias. Utilizaram-se ratos de laboratório macho Wistar, com acesso livre ao alimento, designados a um de dois grupos, e durante dez dias estiveram sob uma dieta alta em gordura (45 % de calorias provenientes de gorduras) ou uma dieta padrão de laboratório. Nos dias 1, 5 e 10, realizou-se uma análise detalhada do comportamento alimentar ao início do período de escuridão. Os resultados mostraram que os sujeitos expostos à dieta alta em gordura acumularam mais gordura corporal e tiveram maior eficiência da alimentação do que o outro grupo, sem aumento do peso corporal nem alterações do padrão da sequência de saciedade comportamental. Isso sugere que a exposição a dietas com alto conteúdo de gordura pode produzir mudanças comportamentais antes de apresentar um ganho de peso excessivo, o que afeta principalmente os mecanismos de controle de eficiência alimentar.

Resumen El consumo excesivo de alimentos con alto contenido de grasas se ha asociado con el incremento de la obesidad. Los efectos fisiológicos y metabólicos del consumo de dietas altas en grasa han sido estudiados extensamente; sin embargo, los mecanismos conductuales asociados al desarrollo de la obesidad por el consumo de estas dietas se han explorado en menor medida. Por tanto, el objetivo del presente estudio fue caracterizar los cambios en los patrones conductuales de la alimentación producidos por el consumo de una dieta alta en grasas durante diez días. Se utilizaron ratas macho Wistar con acceso libre al alimento, asignadas a uno de dos grupos, y durante diez días estuvieron bajo una dieta alta en grasa (45 % de calorías provenientes de grasas) o una dieta estándar de laboratorio. En los días 1, 5 y 10 se realizó un análisis detallado de la conducta alimentaria al inicio del periodo de oscuridad. Los resultados mostraron que los sujetos expuestos a la dieta alta en grasa acumularon más grasa corporal y tuvieron mayor eficiencia de la alimentación que el otro grupo, sin incremento del peso corporal ni alteraciones del patrón típico de la secuencia de saciedad conductual. Esto sugiere que la exposición a dietas con alto contenido de grasas puede producir cambios conductuales antes de que se presente una ganancia de peso excesivo, lo que afecta principalmente los mecanismos de control de eficiencia alimentaria.

Efecto hipofágico de la urocortina en ratas adrenalectomizadas: un análisis de la secuencia de saciedad conductual / Hypophagic effect of urocortin in adrenalectomized rats: An analysis of the behavioral satiety sequence

El objetivo de la presente investigación fue evaluar el efecto de la estimulación de los receptores CRH2 del núcleo paraventricular hipotalámico sobre la ingesta de alimento y la expresión de la secuencia de saciedad conductual (SSC) en ratas adrenalectomizadas. Se trabajó con ocho grupos independientes de ratas Wistar, cuatro grupos adrenalectomizados (ADX) y cuatro con falsa cirugía. A todos los sujetos se les implantó una cánula en el núcleo paraventricular hipotalámico, y se les administró uno de cuatro tratamientos: vehículo, urocortina 2 (UCN2, agonista de CRH2), antisauvagina 30 (antagonista de CRH2), y antisauvagina-30 + UCN2 (pretratamiento). La administración de UCN2 redujo la ingesta de hidratos de carbono y de grasas en las ratas ADX, debido a la interrupción de la SSC; mientras que en las ratas con falsa cirugía, la UCN2 solo disminuyó la ingesta de grasas, debido al adelanto de la SSC. El pretratamiento previno los efectos inducidos en las ratas ADX, pero no en las ratas con falsa cirugía. Estos resultados indican que los receptores CRH2 modularon la ingesta y la SSC en las ratas ADX, lo que constituye un aporte importante en la comprensión de la etiología de la anorexia y del patrón conductual asociado a esta.

The objective of this research was to evaluate the effect of stimulation of receptors CRH2 in the paraventricular nucleus of the hypothalamus on food intake and expression of behavioral satiety sequence (BSS) in adrenalectomized rats. Eight independent groups of Wistar rats were utilized; four adrenalectomized groups (ADX) and four were false surgery. All subjects were implanted with a cannula in the paraventricular nucleus of the hypothalamus and were administered with one of the four treatments: vehicle, urocortin-2 (UCN2, CRH2 agonist), antisauvagine-30 (CRH2 antagonist) or antisauvagine-30 + UCN2 (pretreatment). UCN2 administration reduced intake of carbohydrates and fats in ADX rats due to the interruption of the BSS. In rats with false surgery it decreased fat intake due to the advancement of the BSS. Pretreatment prevented the effects induced by UCN2 in ADX rats but not in rats with false surgery. These results suggest that receptors CRH2 modulated intake and BSS in ADX rats, contributing with relevant information for the understanding of the anorexic ethiology and the behavioral pattern associated to it.

Mild Cognitive Impairment in Patients with Early-Onset Parkinson's Disease.

BACKGROUND/AIMS: Few studies have described mild cognitive impairment (MCI) and cognitive characteristics in early-onset Parkinson's disease (EOPD). This study describes attention/working memory, language, memory, visuospatial abilities, executive function, and frequency of MCI and dementia in EOPD. METHODS: Eighty-one EOPD patients were administered neuropsychological tests and the Beck Depression Inventory. Scores were compared with age/education-appropriate norms and were correlated to years of disease progression and severity of motor symptoms. The frequency of MCI and dementia was determined by the Movement Disorder Society criteria. RESULTS: Thirty-one percent of patients met the MCI criteria, but none had dementia. Commonly affected domains were memory, visuospatial, and executive function. Cognitive dysfunction was not explained by depression or severity of motor symptoms. CONCLUSION: One third of EOPD patients presented with MCI, which was not associated with the same risk factors as reported in late-onset Parkinson's disease. MCI could have a different prognostic value in EOPD.

Effects of CB1 cannabinoid receptor activation in the nucleus accumbens shell on feeding behavior / Efectos de la activación del receptor cannabinoide CB1 en el núcleo accumbens shell sobre la conducta alimentaria / Efeitos da ativação do receptor cannabinóide CB1 no núcleo accumbens shell sobre a conduta alimentar

Obesity and its related pathologies are well- known health hazards. Although obesity and overweight have multifactorial causes, overeating is common in both of these conditions. According to animal models, endocannabinoids and their receptors in the brain play a key role in the genesis and development of obesity. It has been proposed that the cannabinoid receptors CB1 (RCB1) expressed in the nucleus accumbens shell (NAC) are involved in the increase of the hedonic properties of food. To test this hypothesis, this study aimed to assess the effects of activating the NACs RCB1 on standard food intake during the light phase of the light-dark cycle. The effects of activating the RCB1 with CP 55,940 and WIN 55-212-2 (0.125, 0.25 and 0.5 nmol) in the NACS on feeding behavior and the behavioral satiety sequence of rats were assessed. It was found that both agonists increased food intake and delayed expression of satiety during the light phase. These results suggest that cannabinoid agonists encourage food intake when motivation is low and palatability is normal.

La obesidad y sus patologías relacionadas son riesgos de salud muy conocidos. Aunque la obesidad y el sobrepeso tienen causas multifactoriales, la sobreingesta de alimento es frecuente en estas condiciones. De acuerdo con modelos animales, los endocanabinoides y sus receptores en el cerebro juegan un papel clave en la génesis y desarrollo de la obesidad. Se ha propuesto que los receptores a canabinoides CB1 (RCB1) expresados en el núcleo accumbens shell (NAcS) están involucrados en el incremento de las propiedades hedónicas del alimento. Para probar esta hipótesis, este estudio tuvo como objetivo evaluar los efectos de la activación de los RCB1 en el NAcS sobre la ingesta de alimento estándar durante la fase de luz del ciclo luz-oscuridad. Se evaluaron los efectos de la activación de los RCB1 con WIN 55-212-2 y CP 55,940 (0.125, 0.25, y 0.5 nmol) en el NAcS sobre la conducta alimentaria y la secuencia de saciedad conductual en ratas. Se encontró que ambos agonistas aumentaron la ingesta de alimento y demoraron la expresión de la saciedad durante la fase de luz. Lo anterior sugiere que los agonistas canabinoides estimulan el consumo de alimento cuando la motivación por el mismo es baja y la palatabilidad es normal.

A obesidade e suas patologias relacionadas são riscos de saúde muito conhecidos. Ainda que a obesidade e o sobrepeso possuam causas multifatoriais, a sobre ingestão de alimento é frequente nestas condições. De acordo com modelos animais, os endocanabinóides e seus receptores no cérebro jogam um papel chave na gênese e desenvolvimento da obesidade. Foi proposto que os receptores a canabinóides CB1 (RCB1) expressos no núcleo accumbens shell (NAcS) estão envolvidos no aumento das propriedades hedônicas do alimento. Para testar esta hipótese, este estudo teve como objetivo avaliar os efeitos da ativação dos RCB1 nos NAcS sobre a ingestão de alimento padrão durante a fase de luz do ciclo luz-escuridão. Avaliaram-se os efeitos da ativação dos RCB1 com WIN 55-212-2 e CP 55,940 (0.125, 0.25, e 0.5 nmol) no NAcS sobre a conduta alimentar e a sequência de saciedade condutual em ratos. Encontrou-se que ambos agonistas aumentaram a ingestão de alimento e demoraram a expressão da saciedade durante a fase de luz. Isso sugere que os agonistas canabinóides estimulam o consumo de alimento quando a motivação pelo mesmo é baixa e a palatabilidade é normal.

Stimulation of dopamine D4 receptors in the paraventricular nucleus of the hypothalamus of male rats induces hyperphagia: involvement of glutamate.

Obesity is a serious worldwide health problem, affecting 20-40% of the population in several countries. According to animal models, obesity is related to changes in the expression of proteins that control energy homeostasis and in neurotransmission associated to regulation of food intake. For example, it has been reported that diet-induced obesity produces overexpression of dopamine D4 receptor (D4R) mRNA in the ventromedial hypothalamic nucleus (VMH) of mice. Neurons in the VMH send dense glutamatergic projections to other hypothalamic regions as the paraventricular nucleus (PVN), where multiple signals are integrated to finely regulate energy homeostasis and food intake. Although it is well established that dopaminergic transmission in the hypothalamus plays a key role in modulating feeding, the specific mechanisms involved in the activation of D4R in the PVN and its modulatory action on glutamate release and feeding behavior have remained unexplored. To fill this gap, we characterize the behavioral and neurochemical role of D4R in the PVN. In behavioral experiments, we examined the effects of activation of dopamine D4 receptors in the PVN on food intake and on the behavioral satiety sequence in rats exposed to a food-restricted feeding program. In vitro experiments were conducted to study the effects of activation of dopamine D4 receptors on [(3)H]glutamate release and on plasma corticosterone in explants of the PVN. We found that activation of D4R in the PVN induced inhibition of glutamate release and stimulated food intake by inhibiting satiety. Furthermore, activation of D4R in the PVN decreased plasma levels of corticosterone, and this effect was reverted by NMDA. According to our findings, D4R in the PVN may be a target for the pharmacotherapy for obesity as well as eating disorder patients who show restrictive patterns and overweight.

Endogenous content and release of [(3)H]-GABA and [(3)H]-glutamate in the spinal cord of chronically undernourished rat.

The aim of this study was to determine the effect of chronic undernutrition on the content and release of γ-amino butyric acid (GABA) and glutamate (GLU) transmitters in the rat spinal cord. The release of [(3)H]-GABA and [(3)H]-GLU was determined by radioactive liquid scintillation techniques, and the concentrations of GABA and GLU in spinal cord preparations from control and undernourished young rats (50-60 days old) were measured by reverse-phase HPLC. The GABA and GLU contents in the lumbar spinal dorsal horn (L6 segment) were significantly lower in undernourished rats relative to control rats (22.2 ± 3.7 and 10.7 ± 1.9 %, respectively; P < 0.05). Spinal cord blocks from undernourished animals also showed lower rates of [(3)H]-GABA and [(3)H]-GLU release than controls (27.6 ± 3.5 and 12.8 ± 2.5 %, respectively; P < 0.01). We propose that the decreases in GLU content and release are consistent with a reduced activation of either afferent fibers, spinal glutaminergic neurons, or both. Furthermore, we propose that the decreased content and release of GABA in undernourished animals are related to a depression in pre- and post-synaptic inhibition. In addition, we hypothesize that the reductions in GABA content and release serve as compensatory mechanisms to counterbalance decreases in sensory transmission and GLU content in the spinal cord of the chronically undernourished rat.

Role of cannabinoid CB1 receptors on macronutrient selection and satiety in rats.

It has been shown that endogenous and exogenous cannabinoids substantially increase feeding. Despite evidence for a role of endocannabinoids in mediating food ingestion, the mechanisms by which CB1 receptor agonists and antagonists have an effect on motivational processes (hunger, satiety) as well as on specific food preference are not entirely understood. The purpose of this study was to investigate the effects of systemic injection of the CB1 receptor agonist, ACEA, on protein, carbohydrates and fat intake as well as on the behavioural satiety sequence (BSS) in pre-satiated rats. Following a 120-min access to a three pure nutrient diet (protein, carbohydrates and fat) at dark onset, male Wistar rats were injected intraperitoneally with ACEA (0.1, 0.25, 0.5 and 1.0 mg/kg). Immediately after the injection, animals were placed into separate experimental cages with free access to food and a single 60-min period was video recorded to evaluate the BSS; protein, carbohydrates and fat intake (g) was measured at the same period of time. Intake of carbohydrates was significantly increased and this effect was prevented by the pre-treatment with AM 251. Analysis of BSS showed that administration of 0.5 mg/kg of ACEA reversed the satiation induced by food ingestion by increasing the time spent eating and decreasing the time resting without altering the overall activity. The present results suggest that the stimulation of food intake induced by activation of CB1 receptors involves a specific dietary component and behavioural selective mechanisms (stimulating hunger and inhibiting satiety).

The effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence in rats.

The present study examined the effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence (BSS) in rats. The 5-HT1A receptor agonist, 8-OH-DPAT (0.5 microg), and the 5-HT2C receptor agonist, Ro-60-0175 (3.0 microg), were injected into the paraventricular nucleus (PVN) of rats. The animals were maintained on an ad libitum feeding paradigm with access to water and individual sources of protein, carbohydrate, and fat. Intra-PVN administration of each agonist was associated with decreased carbohydrate consumption. The effect was enhanced by the administration of both agonists together. Behavioral analysis indicated that co-administration of 8-OH-DPAT and Ro-60-0175 interrupted the natural BSS with an increase in non-feeding behavior, whereas the 8-OH-DPAT alone promoted early development of the natural BSS. In conclusion, the 5-HT receptor agonists affected serotonergic modulation of feeding behavior in a functionally selective way.

Role of 5-HT1A and 5-HT1B receptors in the hypophagic effect of 5-HT on the structure of feeding behavior.

BACKGROUND: Feeding behavior is deeply affected by serotonergic neurotransmission. This regulatory activity is mediated mainly by specific 5-HT1/2 receptors, and the paraventricular nucleus (PVN) plays a key role in this phenomena. In order to reveal the involvement of 5-HT1A and 5-HT1B receptors in the paraventricular nucleus of the hypothalamus (PVN) on serotonin-induced hypophagia, we examined the effects of intra-PVN injections of serotonin in WAY 100635 or SB 216641-pretreated rats on the structure of feeding behavior. MATERIAL/METHODS: Male Wistar rats were kept at 21+/-1 degrees C with a 12 h light /dark cycle on a self-selection feeding paradigm, provided with freely available and separate sources of protein, carbohydrate, fat and water. Blockade of 5-HT1A or 5-HT1B receptors in the paraventricular nucleus was effected by WAY 100635 (2 microg) or SB-216641 (2 microg) pretreatment; ten minutes later, 5-HT (2 microg) was applied into the same nucleus, then food intake and meal patterns were measured in a 30-minute period. The behavioral test was conducted at the beginning of the dark phase. RESULTS: The suppressive effect of 5-HT on carbohydrate intake was blocked by both WAY 100635 and SB 216641 at the beginning of the active (dark) feeding period. CONCLUSIONS: The hypophagic effect induced by 5-HT requires activation of 5-HT1A and 5-HT1B receptors, and the specific contribution of these subtype receptors is different, since the 5-HT1A subtype showed higher behavioral selectivity.