Understanding the Co-occurrence of Gambling Disorder and Problematic Pornography Use: Exploring Sociodemographic and Clinical Factors.

The co-occurrence between gambling disorder (GD) and problematic pornography use (PPU) has not yet been explored. Therefore, the present study compared (a) sociodemographic variables, (b) GD-related factors, (c) substance use, (d) psychopathology, (e) personality features, (f) impulsivity, and (g) emotion regulation between individuals with GD (GD group) and those with co-occurring GD and PPU (GD+PPU group). The sample consisted of 359 treatment-seeking individuals with GD: n = 332 individuals had GD only (GD group) and n = 37 individuals had GD and co-occurring PPU (GD+PPU group). GD severity, impulsivity, psychopathology, personality, emotion regulation, and other sociodemographic and clinical variables were assessed. No between-group differences in sociodemographic measures were observed. The GD+PPU group demonstrated greater GD severity and a higher likelihood of substance use compared to those without PPU. Furthermore, the presence of PPU was associated with worse psychopathology, higher impulsivity (except for lack of premeditation and positive urgency), more difficulties in emotion regulation (except for non-acceptance of emotions and limited access to emotions), and a personality profile characterized by lower levels of self-directedness and cooperativeness. The co-occurrence of GD and PPU seems associated with a more dysfunctional clinical profile.

Alcohol and energy drinks: individual contribution of common ingredients on ethanol-induced behaviour.

Since energy drinks (EDs) were sold to the general public as soft drinks and recreational beverages, mixing EDs with ethanol has grown in popularity, particularly among younger people. Given the research that links these drinks with higher risk behaviors and increased ethanol intake, ethanol combined with EDs (AmEDs) is a particularly worrying combination. EDs generally commonly include a variety of ingredients. Sugar, caffeine, taurine, and B-group vitamins are almost always present. Studies on the combined effect of ethanol and sugar and caffeine on ethanol-induced behaviors are extensive. Not so much in regards to taurine and vitamins. This review briefly summarises available information from research on the isolated compounds on EtOH-induced behaviors first, and secondly, the combination of AmEDs on EtOH effects. The conclusion is that additional research is needed to fully comprehend the characteristics and consequences of AmEDs on EtOH-induced behaviors.

Perceived Intensity and Palatability of Fatty Culinary Preparations is Associated with Individual Fatty Acid Detection Threshold and the Fatty Acid Profile of Oils Used as Ingredients.

The term oleogustus was recently proposed to describe a sixth basic taste that could guide preference for fatty foods and dishes to an extent. However, experimental data on food preference based on fatty acid (FA) content is scarce. Our aim was to examine the role of FA profile of oils and preparations as well as FA sensory thresholds on the palatability of salty and sweet culinary preparations representative of traditional Spanish Mediterranean cooking. In this study, we used three oils with similar texture and odor profile but different in their FA composition (saturated, monounsaturated, and polyunsaturated) and compared subjects in regard to their FA detection threshold and perceived pleasantness and intensity. Our results indicate that whereas saturated FAs cannot be detected at physiological concentrations, individuals can be categorized as tasters and nontasters, according to their sensory threshold to linoleic acid, which is negatively associated with perceived intensity (r = -0.393, P < 0.001) but positively with palatability (r = 0.246, P = 0.018). These differences may be due to a possible response to a fat taste. This sixth taste, or oleogustus. would allow establishing differences in taste intensity/palatability considering the FA profile of the culinary preparations. Given that tasters can detect linoleic and oleic acid at lower concentrations than nontasters, a greater amount of unsaturated FAs in culinary preparations could provoke an unpleasant experience. This finding could be relevant in the context of the culinary sector and to further our understanding of food preference and eating behavior.

Genome-wide linkage analysis of families with primary hyperhidrosis.

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.

Polyphenols and taste 2 receptors. Physiological, pathophysiological and pharmacological implications.

Polyphenols are phytochemical compounds found mostly in plants with several biological properties. Many of the benefits attributed to fruits and vegetables have been linked to their content in these molecules. As a result, the last decade has witnessed an increase in polyphenol-derived compounds claiming diverse therapeutic properties. Although the mechanism of action of such compounds is yet to be fully disclosed, one of the components that recently has been proposed to participate significantly in the health properties of polyphenols is the type 2 taste receptors (T2Rs). These receptors are responsible for the detection of bitter taste and represent the first line of defence against potentially harmful components in food. The recent discovery of extra-oral T2Rs in several metabolically active tissues has generated intense interest in the potential health impact. Given that most phenolic molecules taste bitter, exploring the T2Rs as a putative pharmacological target for the development of plant-based drug therapies is a promising field of research. Some T2Rs are involved in the control of cilia beat frequency and smooth muscle relaxation in the air tract together with leukocyte homeostasis, important events disrupted in the high prevalence of respiratory diseases. Furthermore, T2Rs are involved in nutrient-gut interactions to modulate gut hormones that influence gastrointestinal motility, appetite and glycemia. Thus, this commentary focuses on the latest novelty advances in relation to the peripheral expression of T2Rs, and polyphenols and T2Rs relationship from a therapeutic point of view.

Salivary endocannabinoids as mediators in the relationship between omega-6 and omega-3 fatty acid ratio intake from highly-processed foods and anthropometric markers of health in women.

Data suggest that a high ω6 to ω3 ratio (ω6:ω3) contributes to obesity. Highly processed foods are a common source of high ω6:ω3 and have also been associated with increased cardiovascular risk. We hypothesised that salivary endocannabinoids (eCBs) act as a mediator between ω6:ω3 from highly processed foods and anthropometric markers of cardiovascular risk. Finally, we explored sex differences on these parameters. Participants filled a self-report intake frequency inventory. Body measurements were registered, and fasted saliva was collected and analysed using LC/MRM. Overweight subjects consuming more highly processed foods, but not those consuming more whole foods, presented an increased ω6:ω3 and salivary eCB levels. Also, the ω6:ω3 ratio in participants consuming highly processed but not whole foods predicted eCB levels in overweight women. Finally, we show that salivary eCBs correlate with body composition in women only. Our study shows that the food source has a differential impact on physiological and behavioural aspects of food intake.

Cannabinoids, Chemical Senses, and Regulation of Feeding Behavior.

The herb Cannabis sativa has been traditionally used in many cultures and all over the world for thousands of years as medicine and recreation. However, because it was brought to the Western world in the late 19th century, its use has been a source of controversy with respect to its physiological effects as well as the generation of specific behaviors. In this regard, the CB1 receptor represents the most relevant target molecule of cannabinoid components on nervous system and whole-body energy homeostasis. Thus, the promotion of CB1 signaling can increase appetite and stimulate feeding, whereas blockade of CB1 suppresses hunger and induces hypophagia. Taste and flavor are sensory experiences involving the oral perception of food-derived chemicals and drive a primal sense of acceptable or unacceptable for what is sampled. Therefore, research within the last decades focused on deciphering the effect of cannabinoids on the chemical senses involved in food perception and consequently in the pattern of feeding. In this review, we summarize the data on the effect of cannabinoids on chemical senses and their influences on food intake control and feeding behavior.

Drug-free and context-dependent locomotor hyperactivity in DBA/2 J mice previously treated with repeated cocaine: Relationship with behavioral sensitization and role of noradrenergic receptors.

Drug-associated contexts and discrete cues can trigger motivational states responsible for drug-seeking behavior and relapse. In preclinical research, drug-free conditioned hyperactivity has been used to investigate the expression of memories associated with psychostimulant drug effects. Addictive drugs can produce long-lasting sensitization to their psychomotor actions, a phenomenon known as behavioral sensitization. The neuroplasticity underlying behavioral sensitization appears to be involved in pathological drug pursuit and abuse. In the present study we evaluated drug-free, context-dependent hyperactivity in DBA/2 J mice previously treated with cocaine and we explored whether this conditioned effect was related to behavioral sensitization. Given the role of noradrenergic (NA) neurotransmission in memory retrieval, consolidation and reconsolidation processes, we also investigated whether conditioned hyperactivity in a drug-free state was mediated by NA receptors. Animals underwent a sensitization protocol with six cocaine injections (0, 5, 10 or 20 mg/kg) paired to a particular floor cue. Three days after this sensitization phase, all animals were exposed to the same familiar floor environment without drug treatment. A second test with an unfamiliar floor was conducted 24 h later. Conditioned hyperactivity was also explored after one or three cocaine pairings and was evaluated for its duration (with repeated familiar vs. unfamiliar floor tests). In a series of pharmacological experiments, we evaluated the effects propranolol (a non-selective antagonist of ß1- and ß2-receptors) and prazosin (α1-receptor antagonist) on conditioned hyperactivity. Cocaine treatment produced both robust sensitization and drug-free conditioned hyperactivity, an effect that lasted up to 17 days (with cocaine 20 mg/kg). A significant correlation between the magnitude of cocaine sensitization and the level of conditioned hyperactivity was found. Propranolol, but not prazosin, blocked context-dependent hyperlocomotion in a drug-free state. Our data, together with a vast body of literature, indicate that the NA system plays a key role in the retrieval and behavioral expression of drug-associated memories.

Basal Levels of Salivary Alpha-Amylase Are Associated with Preference for Foods High in Sugar and Anthropometric Markers of Cardiovascular Risk.

Salivary alpha-amylase (sAA) influences the perception of taste and texture, features both relevant in acquiring food liking and, with time, food preference. However, no studies have yet investigated the relationship between basal activity levels of sAA and food preference. We collected saliva from 57 volunteers (63% women) who we assessed in terms of their preference for different food items. These items were grouped into four categories according to their nutritional properties: high in starch, high in sugar, high glycaemic index, and high glycaemic load. Anthropometric markers of cardiovascular risk were also calculated. Our findings suggest that sAA influences food preference and body composition in women. Regression analysis showed that basal sAA activity is inversely associated with subjective but not self-reported behavioural preference for foods high in sugar. Additionally, sAA and subjective preference are associated with anthropometric markers of cardiovascular risk. We believe that this pilot study points to this enzyme as an interesting candidate to consider among the physiological factors that modulate eating behaviour.

Psychometric Properties of the German Translated Version and Adaptation of the Food Craving Inventory.

Dysfunctional eating behavior is a major risk factor for developing all sorts of eating disorders. Food craving is a concept that may help to understand better why and how these and other eating disorders become chronic conditions through non homeastatically-driven mechanisms. As obesity affects people worldwide, cultural differences must be acknowledged to apply proper therapeutic strategies. In this work, we adapted the Food Craving Inventory (FCI) to the German population. We performed a factor analysis of an adaptation of the original FCI in a sample of 326 men and women. We could replicate the factor structure of the FCI on a German population. The factor extraction procedure produced a factor solution that reproduces the four factors described in the original inventory, the FCI. Our instrument presents high internal consistency, as well as a significant correlation with measures of convergent and discriminant validity. The FCI-Deutsch (FCI-DE) is a valid instrument to assess craving for particular foods in Germany, and it could, therefore, prove useful in the clinical and research practice in the field of obesity and eating behaviors.

Role of Endocannabinoids on Sweet Taste Perception, Food Preference, and Obesity-related Disorders.

The prevalence of obesity and obesity-related disorders such as type 2 diabetes (T2D) and metabolic syndrome has increased significantly in the past decades, reaching epidemic levels and therefore becoming a major health issue worldwide. Chronic overeating of highly palatable foods is one of the main responsible aspects behind overweight. Food choice is driven by food preference, which is influenced by environmental and internal factors, from availability to rewarding properties of food. Consequently, the acquisition of a dietary habit that may lead to metabolic alterations is the result of a learning process in which many variables take place. From genetics to socioeconomic status, the response to food and how this food affects energy metabolism is heavily influenced, even before birth. In this work, we review how food preference is acquired and established, particularly as regards sweet taste; towards which flavors and tastes we are positively predisposed by our genetic background, our early experience, further lifestyle, and our surroundings; and, especially, the role that the endocannabinoid system (ECS) plays in all of this. Ultimately, we try to summarize why this system is relevant for health purposes and how this is linked to important aspects of eating behavior, as its function as a modulator of energy homeostasis affects, and is affected by, physiological responses directly associated with obesity.

Transcranial Magnetic Stimulation on Rodent Models.

Transcranial magnetic stimulation (TMS) is a non-invasive method that can be used as an interventional technique to investigate causality in the brain-behavior relationship, through depolarization or hyperpolarization in the neurons of the brain. Different techniques of TMS can be used to investigate causality in the brain-behavior relationship. The behavioral effects induced by TMS are complex since it has been shown that the performance in the same cognitive task can be either facilitated or inhibited depending on the area being stimulated. To date, most studies involving TMS are focused mainly on the facilitation properties of this technique. It is used to treat a wide-range of neurological and psychiatric conditions such as depression, ischemia, Alzheimer's disease, or motor impairment. Interestingly, TMS can be used to induce a virtual lesion that could provide a valuable and much needed model of cognitive impairments in early preclinical development. This review describes the existing TMS paradigms in rodents and the major challenges that were encountered by the researchers as the method was translated from clinical to preclinical applications. In summary, the existing knowledge gained in animal research emphasizes the necessity to investigate new TMS paradigms in the preclinical setting and its effects.

Implications of glial nitric oxide in neurodegenerative diseases.

Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

Retinal aging in the diurnal Chilean rodent (Octodon degus): histological, ultrastructural and neurochemical alterations of the vertical information processing pathway.

The retina is sensitive to age-dependent degeneration. To find suitable animal models to understand and map this process has particular importance. The degu (Octodon degus) is a diurnal rodent with dichromatic color vision. Its retinal structure is similar to that in humans in many respects, therefore, it is well suited to study retinal aging. Histological, cell type-specific and ultrastructural alterations were examined in 6-, 12- and 36-months old degus. The characteristic layers of the retina were present at all ages, but slightly loosened tissue structure could be observed in 36-month-old animals both at light and electron microscopic levels. Elevated Glial fibrillary acidic protein (GFAP) expression was observed in Müller glial cells in aging retinas. The number of rod bipolar cells and the ganglion cells was reduced in the aging specimens, while that of cone bipolar cells remained unchanged. Other age-related differences were detected at ultrastructural level: alteration of the retinal pigment epithelium and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and often differed in morphology from those in the young animals. These results support our hypothesis that (i) the rod pathway seems to be more sensitive than the cone pathway to age-related cell loss; (ii) structural changes in the basement membrane of pigment epithelial cells can be one of the early signs of degenerative processes; (iii) the loss of synaptic proteins especially from those of the ribbon synapses are characteristic; and (iv) the degu retina may be a suitable model for studying retinal aging.

Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus.

Memory loss is one of the key features of cognitive impairment in either aging, Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for memory loss are today focused on addressing symptomatology. One of these approved compounds is memantine, a partial NMDA receptor antagonist that has proved its beneficial effects in cognition. The Octodon degus (O. degus) has been recently proposed as a potential model relevant for neurodegenerative diseases. However, there are no previous studies investigating the effect of pharmacological treatments for age-related cognitive impairment in this rodent. In this work we aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced memory impairment in young and old O. degus. Young and old animals were trained in different behavioral paradigms validated for memory evaluation, and randomly assigned to a control (CTL, n=14) or an SD (n=14) condition, and treated with vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that SD impairs memory in both young and old animals, although the effect in the old group was significantly more severe (P<0.05). Memantine pretreatment was able to prevent the cognitive impairment caused by SD in both age groups, while it had no negative effect on CTL animals. The positive effect of memantine in counteracting the negative effect of SD on the retrieval process even in the aged O. degus further supports the translational potential of both the challenge and the species, and will enable a better understanding of the behavioral features of memantine effects, especially related with reference and working memories.

Octodon degus: a model for the cognitive impairment associated with Alzheimer's disease.

Octodon degus (O. degus) is a diurnal rodent that spontaneously develops several physiopathological conditions, analogous in many cases to those experienced by humans. In light of this, O. degus has recently been identified as a very valuable animal model for research in several medical fields, especially those concerned with neurodegenerative diseases in which risk is associated with aging. Octodon degus spontaneously develops ß-amyloid deposits analogous to those observed in some cases of Alzheimer's disease (AD). Moreover, these deposits are thought to be the key feature for AD diagnosis, and one of the suggested causes of cell loss and cognitive deficit. This review aims to bring together information to support O. degus as a valuable model for the study of AD.

Dantrolene blockade of ryanodine receptor impairs ethanol-induced behavioral stimulation, ethanol intake and loss of righting reflex.

Calcium has been characterized as one of the most ubiquitous, universal and versatile intracellular signals. Among other substances with the ability to alter intracellular calcium levels, ethanol has been described as particularly relevant because of its social and economic impact. Ethanol effects on calcium distribution and flux in vitro have been widely studied, showing that acute ethanol administration can modulate intracellular calcium concentrations in a dose dependent manner. Intracellular calcium released from the endoplasmic reticulum plays a determinant role in several cellular processes. In this study, we aim to assess the effect of dantrolene, a ryanodine receptor antagonist, on three different ethanol-elicited behaviors: locomotor activity, loss of righting reflex and ethanol intake. Mice were challenged with an injection of dantrolene (0-5 mg/kg, i.p.) 30 min before ethanol (0-4 g/kg, i.p.) administration. Animals were immediately placed in an open field cylinder to monitor distance travelled horizontally or in a V-shaped trough to measure righting reflex recovery time. For ethanol intake, dantrolene (0-5mg/kg, i.p.) was administered 30 min before ethanol (20%, v/v) exposure, following a drinking in the dark paradigm. Our results showed that dantrolene selectively reduces ethanol-induced stimulation, loss of righting reflex, and ethanol intake in a dose dependent manner. Together, these data suggest that intracellular calcium released from the endoplasmic reticulum may play a critical role in behavioral effects caused by ethanol, and point to a calcium-dependent pathway as a possible cellular mechanism of action for ethanol.

Ethanol drinking-in-the-dark facilitates behavioral sensitization to ethanol in C57BL/6J, BALB/cByJ, but not in mu-opioid receptor deficient CXBK mice.

BACKGROUND: Neuroplasticity associated with drug-induced behavioral sensitization has been associated with excessive drug pursuit and consumption characteristic of addiction. Repeated intraperitoneal (ip) injections of ethanol (EtOH) can induce psychomotor sensitization in mice. In terms of its clinical relevance, however, it is important to determine whether this phenomenon can also be produced by voluntary EtOH consumption. METHODS: The present investigation used a drinking-in-the-dark (DID) methodology to induce high levels of EtOH drinking in mice; EtOH replaces water for 2 or 4h, starting 3h after the beginning of the dark cycle. Animals followed a 3-week DID protocol prior to an evaluation of EtOH-induced locomotor activity (acute and repeated EtOH). For the first week, animals had access to 20% EtOH. On weeks 2 and 3, different concentrations of EtOH (10, 20 or 30%) were used. Three different inbred strains of mice were used: C57BL/6J (B6), BALB/cByJ (BALB), and CXBK. The CXBK mouse line was used because of its reduced expression and functioning of brain mu-opioid receptors, which have been suggested to participate in the development of EtOH-induced sensitization. B6 and BALB mice were used as controls. RESULTS: B6 and CXBK mice presented comparable levels of EtOH drinking (approx. 3g/kg in 2h), that were higher than those showed by BALB. All animals, regardless of genotype, adjusted volume of EtOH intake to obtain stable g/kg of EtOH across concentrations. Previous EtOH DID produced (B6) or potentiated (BALB) sensitization to EtOH; this effect was not seen in CXBK. Western blot analysis showed a reduced number of mu-opioid receptors in several brain regions of CXBK as compared to that of B6 and BALB mice. CONCLUSIONS: In summary, here we show that the DID methodology can be used to trigger EtOH-induced neuroplasticity supporting psychomotor sensitization, a process that might require participation of mu-opioid receptors.