Paralysis of the trapezius muscle: evaluation and surgical management.

Background: Paralysis of the trapezius muscle most commonly results from iatrogenic injury to the spinal accessory nerve. Methods: The clinical presentation and physical examination findings of trapezius palsy have been well characterized, but unfortunately the diagnosis of this condition is oftentimes missed or delayed, sometimes leading to unnecessary surgery on the rotator cuff or tendon of the long head of the biceps. Results: The diagnosis can be confirmed using electromyography with nerve conduction studies. Although nonoperative treatment may help some patients with temporary neurapraxia of the spinal accessory nerve, nerve repair with or without nerve grafting should be performed soon for patients suspected of a nerve transection. Nerve transfers can be considered within the first year after the injury when nerve repair and grafting cannot be completed. For chronic trapezius palsy, transfer of the levator scapulae and rhomboids has been refined and represents a very successful surgical procedure. Rarely, scapulothoracic arthrodesis is considered for individuals with failed tendon transfers or multiple nerve involvement. Conclusion: Trapezius palsy is oftentimes missed. An accurate diagnosis allows consideration of various treatment modalities that have been reported to provide good outcomes for properly selected patients.

COMPARISON OF LIGAMENT Z-PLASTY AND CONVENTIONAL SURGERY FOR THE TREATMENT OF CARPAL TUNNEL SYNDROME. A RANDOMIZED CLINICAL TRIAL.

BACKGROUND: Conventional surgery performed to treat carpal tunnel syndrome (CTS) is associated with complications such as pillar pain or loss of strength. This study aimed to compare the incidence of pillar pain between two techniques at the 3-week and 6-month follow-up and to determine any differences in the recovery of grip strength (GS), pinch strength (PS), and Boston Carpal Tunnel Questionnaire (BCTQ) scores. METHODS: This randomized clinical trial comprised 109 patients of which 55 underwent ligament Z-plasty and 54 underwent conventional surgery (longitudinal section of the transverse carpal ligament without posterior closure). The GS, PS, presence of pillar pain, and BCTQ scores were assessed preoperatively and after 3 weeks and 6 months. RESULTS: The incidence of pillar pain after 3 weeks was lower in patients undergoing Z-plasty than in those undergoing conventional surgery (25.5% vs. 44.4%, p = 0.04). Moreover, the absolute change in the PS after 3 weeks (p = 0.01) and GS after 6 months (p = 0.05) and the absolute and relative changes in the PS after 6 months (p = 0.008 and p = 0.01, respectively) were significantly higher in the Z-plasty group than in the conventional surgery group. CONCLUSIONS: Z-plasty is a valid surgical procedure for treating CTS. It is associated with a lower incidence of pillar pain and better recovery of postoperative strength compared to the conventional surgical technique, with both techniques showing similar results in CTS recovery.

Reverse Shoulder Arthroplasty for Proximal Humerus Fractures: A Review of Current Evidence.

PURPOSE OF REVIEW: The aim of this review is to summarize information published in the recent peer-reviewed literature on reverse shoulder arthroplasty (RSA) for proximal humerus fractures. RECENT FINDINGS: Although there is still some debate regarding which may be the best treatment for proximal humerus fractures in certain age ranges, RSA seems to offer more predictable results than other surgical treatments for elderly patients. Successful tuberosity healing seems to correlate with better outcomes. Recent trends indicate interest in cementless fixation, fracture-specific stems and a 135-degree polyethylene opening angle. RSA provides a successful surgical solution for selected proximal humerus fractures. Indications, design features, and surgical execution have continued to evolve over the last few years.

Glucose 6 phosphate dehydrogenase overexpression rescues the loss of cognition in the double transgenic APP/PS1 mouse model of Alzheimer's disease.

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-ß (Aß) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aß is pivotal in cognitive preservation. Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aß-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aß in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.

Stress inoculation during adolescence attenuates social stress-induced increase in ethanol intake in adult male mice.

Social stress exposure heightens the risk of substance abuse disorder development, especially when endured during adolescence, influencing long-term mental health. This study investigates early-life stress's potential to confer resilience against later-life stressors. To investigate this hypothesis, we examined the impact of a single social defeat (SD) incident during adolescent mice's lives on subsequent voluntary ethanol consumption following repeated adult social stress exposure. Half of the adolescent mice experienced SD at postnatal day 28. Three weeks later (postnatal day 49), defeated groups encountered four confrontations with aggressive residents every 72 h, while control groups were exposed to non-resident exploration. A day after the last SD, defeated mice were classified as resilient or susceptible based on their response to a social interaction test (SIT), a model for depressive behavior. To assess ethanol consumption during young adulthood, researchers used the 'drinking in the dark' and oral ethanol self-administration paradigms. Stress inoculation (IS) slightly increased resilient animals in the SIT. In mice without IS exposure during adolescence, susceptible defeated mice displayed higher ethanol consumption and motivation than control and resilient mice. IS in adolescence effectively counteracted this effect, as IS-SD groups, whether resilient or susceptible, showed no increase in ethanol intake. These groups also exhibited similar motivation to control, measured by the progressive ratio. Notably, elevated IL-6 levels seen in SD-S mice were absent in IS-exposed mice. Additionally, IS-exposed groups had lower prefrontal cortex IL-6 and CX3CL1 levels. These findings support the hypothesis that IS, induced by moderate-intensity stress during adolescence, can enhance resilience to more severe stressors in adulthood.

Subacromial Balloon Spacer Does Not Reduce the Retear Rate for Massive Rotator Cuff Tears: A Comparative Study.

PURPOSE: To determine whether a subacromial spacer decreases the recurrent rotator cuff tear rate in arthroscopically managed massive rotator cuff tears (MRCTs) with 1 year of follow-up. METHODS: We selected all patients who met the following criteria: (1) an MRCT excluding Collin type A, (2) Goutallier stage equal or less than 2, and (3) complete arthroscopic repair of the MRCT. Patients were allocated into 2 groups: A (without subacromial spacer) or B (with subacromial spacer) for a prospective evaluation 1 year after surgery. The primary outcome was the retear rate, determined with magnetic resonance imaging (MRI) according to the classification of Sugaya. Secondary outcome measures were the functional outcomes using visual analog score, Shoulder Subjective Value, and Constant-Murley Score. Preoperative rotator cuff characteristics such as number of tendons involved and the tear retraction also were evaluated. Patient-related data such as sex, age, laterality, history of smoking, and diabetes mellitus were analyzed. RESULTS: In total, 31 patients were included in group A and 33 in group B. Preoperatively, only 2 differences were found between both groups: a significant (but not clinical) greater Constant score in group A (P = .034) and a slightly greater retraction of the supraspinatus in group B (P = .0025). The overall retear rate between the 2 groups was similar regarding the number of patients (P = .746) and the total number of tendons involved in the recurrent tear (P = .112). At 1-year follow-up, no differences were found in VAS (P = .397), SSV (P = .309), and Constant score (P = .105). CONCLUSIONS: In reparable massive rotator cuff tears (excluding Collin type A), the augmentation of repair with a subacromial spacer did not significantly reduce the number of patients with recurrent rotator cuff tears identified by MRI. It was also ineffective in reducing the number of re-ruptured tendons in these patients. No patient-reported or clinically significant findings were noted in Constant, SSV, and VAS scores at 1-year postoperative follow-up. Patients with MRI findings of a healed rotator cuff (Sugaya 1-3) had better clinical outcomes compared with those without. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Voluntary wheel running during adolescence prevents the increase in ethanol intake induced by social defeat in male mice.

RATIONALE: Exposure to social defeat (SD) induces a depressive phenotype, increased ethanol seeking and consumption, accompanied by activation of the neuroinflammatory response. However, a resilient response can be potentiated through physical exercise in the form of voluntary wheel running (VWR) during or after exposure to social stress. Therefore, the aim of this study was to test whether physical exercise during adolescence prior to being exposed to SD can enhance resilience to the increase in ethanol intake. METHODS: Male mice had access to VWR during adolescence and the effects of social defeat (4 sessions every 72 h) on oral ethanol self-administration (SA) was evaluated. Based on the social interaction test, mice were classified as resilient or susceptible to depressive-like behavior. Two weeks after the last encounter, mice were subjected to the drinking in the dark and oral ethanol SA paradigms. Mice were then sacrificed to measure brain-derived neurotrophic factor (BDNF) levels in the striatum and hippocampus. RESULTS: As expected, susceptible mice increased ethanol intake in the oral SA protocol. However, susceptible mice in the exercise condition did not increase ethanol intake, showing similar consumption and motivation for ethanol than the control and resilient groups. On the other hand, decreased BDNF levels were observed in susceptible mice in both experimental conditions compared to the control groups after ethanol SA. CONCLUSIONS: The pre-exposure of VWR prevented the increase in consumption and motivation for ethanol induced by SD in susceptible mice. On the other hand, it appears that VWR did not exhibit any significant long-term effects on BDNF signaling, which is mainly affected in susceptible mice after ethanol intake.

Glenohumeral Arthropathy After Arthroscopic Surgery for Shoulder Instability: Outcomes at 16-Year Follow-up.

Background: Glenohumeral arthropathy after surgery for traumatic shoulder instability is a condition whose etiology and long-term course are still unknown. Purpose: To evaluate the risk factors for the onset of arthropathy and to assess the relationship between the degree of arthropathy and final outcomes. Study Design: Case series; Level of evidence, 4. Methods: We included patients who underwent surgery for a shoulder instability at a single institution between 2000 and 2004. The following variables were studied for relationship with functional outcomes: sex, age, body mass index, smoking at the time of surgery, number of episodes of shoulder dislocation, and time from first dislocation to surgery. The number of anchors used and their position were also evaluated. Functional outcomes were assessed using the Constant-Murley, Western Ontario Shoulder Instability Index, and Rowe scores, and results were compared with the onset of arthropathy according to Buscayret classification. Spearman and Pearson correlations were performed for the association between glenohumeral arthritis (Buscayret grade) and the study variables, the Mann-Whitney U test and Student t test were used to compare outcome scores with the study variables, and the Kruskal-Wallis test was used to compare Buscayret grade and outcome scores. Results: A total of 26 shoulders in 25 patients were analyzed, finding a high rate (54%) of arthropathy at a minimum follow-up of 16 years. Patients with Buscayret grade 4 had the worst functional results (P = .007). However, 80% of patients with Buscayret grade ≤3 had excellent Constant-Murley scores. A significant relationship was found between degree of arthropathy and patients who were smokers before surgery (P < .01). No relationship was found between the onset of arthropathy and the other variables analyzed. Conclusion: Postinstability glenohumeral arthropathy was not correlated with functional outcomes except in those patients with advanced arthroplasty (Buscayret grade 4). A direct relationship was found between smoking before surgery and the onset of glenohumeral arthropathy.

Effect of Voluntary Wheel-Running Exercise on the Endocrine and Inflammatory Response to Social Stress: Conditioned Rewarding Effects of Cocaine.

The present paper evaluates the effect of physical activity on the increase of the conditioned rewarding effects of cocaine induced by intermittent social stress and on the neuroinflammatory response that contributes to the enhancement of drug response. For that purpose, three studies were designed in which social stress was induced in different samples of mice through a social-defeat protocol; the mice underwent an increase of physical activity by different modalities of voluntary wheel running (continuous and intermittent access). The results showed that continuous access to running wheels prior to stress enhanced the establishment of cocaine place preference, whereas an intermittent access exerted a protective effect. Wheel running contingent to cocaine administration prevented the development of conditioned preference, and if applied during the extinction of drug memories, it exerted a dual effect depending on the stress background of the animal. Our biological analysis revealed that increased sensitivity to cocaine may be related to the fact that wheel running promotes inflammation though the increase of IL-6 and BDNF levels. Together, these results highlight that physical exercise deeply impacts the organism's response to stress and cocaine, and these effects should be taken into consideration in the design of a physical intervention.

Resilience to social defeat stress in adolescent male mice.

Adverse social experiences during adolescence are associated with the appearance of mental illness in adulthood. Social defeat (SD) is an ethologically valid murine model to study the consequences of social stress. In adolescent mice, SD induces depressive-like behaviors, increased anxiety and potentiates the reinforcing effects of cocaine and alcohol. However, not all mice exposed to SD will be susceptible to these effects. Adult mice resilient to the effects of SD show a consistent phenotype being resilient to depressive-like behaviors and to the increase in cocaine and alcohol consumption. The aim of the present study was to characterize the resilient phenotype to depressive-like behaviors and increase cocaine and ethanol rewarding effects of mice socially defeated during adolescence. To that end, adolescent mice were exposed to repeated SD, and 24 h after the last encounter, they underwent a social interaction test (SIT) in order to evaluate depressive-like behaviors. Cocaine-induced reward conditioning and ethanol intake was evaluated in two different sets of mice 3 weeks after the last SD using cocaine-induced conditioned place preference (CPP) and oral ethanol self-administration (SA). The neuroinflammation response was measured at the end of the experimental procedure by measuring striatal and cortical levels of IL-6 and CX3CL1. The results confirmed that a comparable percentage of adolescent mice develop resilience to depressive-like behaviors to that observed in adult mice. However, increased anxiety was more severe in resilient mice. Likewise, an increased preference for an ineffective dose of cocaine and an increased ethanol consumption was observed in resilient mice compared to controls. The increase in IL-6 and CX3CL1 was mainly observed in the striatum of susceptible mice compared to that of control mice. Our results confirm that, contrary to prior assumptions in adults, responses to SD stress are more complex and singular in adolescents, and caution should be taken for the correct interpretation and translation of those phenotypes.

Cognitive profile of male mice exposed to a Ketogenic Diet.

In recent years, nutritional interventions for different psychiatric diseases have gained increasing attention, such as the ketogenic diet (KD). This has led to positive effects in neurological disorders such as Parkinson's disease, addiction, autism or epilepsy. The neurobiological mechanisms through which these effects are induced and the effects in cognition still warrant investigation, and considering that other high-fat diets (HFD) can lead to cognitive disturbances that may affect the results achieved, the main aim of the present work was to evaluate the effects of a KD to determine whether it can induce such cognitive effects. A total of 30 OF1 male mice were employed to establish the behavioral profile of mice fed a KD by testing anxiety behavior (Elevated Plus Maze), locomotor activity (Open Field), learning (Hebb Williams Maze), and memory (Passive Avoidance Test). The results revealed that the KD did not affect locomotor activity, memory or hippocampal-dependent learning, as similar results were obtained with mice on a standard diet, albeit with increased anxiety behavior. We conclude that a KD is a promising nutritional approach to apply in research studies, given that it does not cause cognitive alterations.

Effects of ketosis on cocaine-induced reinstatement in male mice.

In recent years, the benefits of the ketogenic diet (KD) on different psychiatric disorders have been gaining attention, but the substance abuse field is still unexplored. Some studies have reported that palatable food can modulate the rewarding effects of cocaine, but the negative metabolic consequences rule out the recommendation of using it as a complementary treatment. Thus, the main aim of this study was to evaluate the effects of the KD on cocaine conditioned place preference (CPP) during acquisition, extinction, and reinstatement. 41 OF1 male mice were employed to assess the effects of the KD on a 10 mg/kg cocaine-induced CPP. Animals were divided into three groups: SD, KD, and KD after the Post-Conditioning test. The results revealed that, while access to the KD did not block CPP acquisition, it did significantly reduce the number of sessions required to extinguish the drug-associated memories and it blocked the priming-induced reinstatement.

Intraoperative pulmonary embolism in shoulder arthroscopy in a patient with previous SARS-CoV-2 infection: a case report.

The objective of this article is to describe intraoperative pulmonary embolism during shoulder arthroscopy in a patient with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, we describe how the pandemic has influenced the population by increasing the rate of embolisms. Awareness of such cases will help to increase knowledge regarding SARS-Cov-2 and to determine if such patients should receive routine antithrombotic prophylaxis.

Impact of adolescent methamphetamine use on social cognition: A human-mice reverse translation study.

BACKGROUND: Methamphetamine dependence is associated with social cognition deficits that may underpin negative social outcomes. However, there are considerable inter-individual differences in social cognition within people with methamphetamine dependence, with age of onset of methamphetamine use being a potential contributing factor. MATERIALS AND METHODS: We conducted two sequential studies examining the link between age of onset of methamphetamine use (adolescence versus young adulthood) and performance in social cognition tests: (1) a human cross-sectional study in 95 participants with methamphetamine dependence varying in age of onset (38 with adolescent onset and 57 with adult onset) and 49 drug-naïve controls; (2) a mice study in which we tested the effects of methamphetamine exposure during adolescence versus young adulthood on social interaction and aggression, and their potential neurochemical substrates in the striatal dopaminergic system. RESULTS: We initially showed that people with methamphetamine dependence who started use in adolescence had higher antisocial beliefs (p = 0.046, Cohen's d=0.42) and worse emotion recognition (p = 0.031, Cohen's d=0.44) than those who started use during adulthood. We reasoned that this could be due to either social cognition deficits leading to earlier onset of methamphetamine use, or methamphetamine-induced neuroadaptive effects specific to adolescence. Mice experiments showed that methamphetamine exposure during adolescence specifically decreased social investigation during social interaction and upregulated striatal tyrosine hydroxylase (p < 0.05, Bonferroni corrected). There was no evidence of adolescent-specific methamphetamine effects on aggression or other measures of dopaminergic function. CONCLUSION: Together, translational findings demonstrate heightened sensitivity to methamphetamine effects on social cognition during adolescence.

Prepulse inhibition can predict the motivational effects of cocaine in female mice exposed to maternal separation.

The prepulse inhibition (PPI) of the startle response can identify the rodents that are more sensitive to the effects of cocaine. Mice with a lower PPI presented a higher vulnerability to the effects of cocaine and a higher susceptibility to developing a substance use disorder (SUD). Maternal separation with early weaning (MSEW) is a relevant animal model to induce motivational alterations throughout life. Nevertheless, only a few studies on females exist, even though they are more vulnerable to stress- and cocaine-related problems. Hence, the aim of the present study was to evaluate the ability of PPI to identify females with a greater vulnerability to the long-term consequences of early stress on the motivational effects of cocaine. Female mice underwent MSEW and were classified according to their high or low PPI. They were then assessed in the cocaine-induced locomotor sensitization test, the conditioned place preference paradigm or the operant self-administration paradigm. Additionally, they were also evaluated in the passive avoidance task, the tail-suspension and the splash tests. The results revealed that the females with lower PPI presented higher consequences of MSEW on the effects of cocaine and showed an increase in anhedonia-like behaviours. Our findings support that a PPI deficit could represent a biomarker of vulnerability to the effects of cocaine induced by MSEW.

Ethanol intake in male mice exposed to social defeat: Environmental enrichment potentiates resilience.

Large preclinical evidence shows that exposure to social defeat (SD) increases vulnerability to drug abuse, increasing the consumption of ethanol. However, not all subjects are equally affected by the changes induced by stress. Previous reports have evidenced that the resilient phenotype to depressive-like behaviors after SD is associated with the resistant phenotype to cocaine-increased rewarding effects and the smaller neuroinflammatory response. The aim of the present study was to further clarify whether the resilient profile to depressive-like behavior also predicts a protection against the increase in ethanol intake induced by SD. The neuroinflammatory profile was studied after the end of the oral ethanol self-administration (SA) procedure, measuring levels of the pro-inflammatory cytokine IL-6 and the chemokine CX3CL1 or fractalkine in the striatum and prefrontal cortex. Previous studies have shown that environmental enrichment (EE) is an effective mechanism to dimish the detrimental effects of social stress. In a second study, we aimed to evaluate if EE housing before exposure to SD could potentiate resilience. Our results showed that mice with a phenotype susceptible to SD-induced depressive-like behaviors showed increased ethanol consumption and increased neuroinflammatory signaling. In contrast, despite the lack of effect on depressive-like behaviors, defeated mice previously housed under EE conditions did not show an increase in ethanol SA or an increase in immune response. To sum up, the resilient phenotype to SD develops at different levels, such as depressive-like behaviors, ethanol consumption and the neuroinflammatory response. Our results also point to the protective role of EE in potentiating resilience to SD effects.

Reverse shoulder arthroplasty in complex fractures of the proximal humerus: results after 7 years of follow-up.

BACKGROUND: There is still little information about the long-term results of clinical and radiological evolution in patients older than 65 years with complex proximal humerus fractures (CPHF) treated acutely with reverse shoulder arthroplasty (RSA). The aim of this paper was to evaluate function and results 7 years after surgery. MATERIAL AND METHODS: A prospective cross-sectional cohort study was designed for this purpose. Patients who underwent RSA surgery during 2012 because of a CPHF were included. The surgical approach was randomized (deltopectoral vs anterosuperior). Functional activity, evolution of tuberosities and evidence of scapular notching 7 years after surgery were analyzed. RESULTS: After evaluating 32 patients, the Constant score improved from 64.83 in the first year to 69.54 at 7 years postoperative. Results were independent of the approach used. Functional outcomes were poorer in patients with scapular notching and when tuberosities were resorbed or displaced. CONCLUSIONS: At 7 years, function in patients undergoing RSA after CPHF demonstrated improvement in all patients except those who developed scapular notching or when tuberosities did not consolidate in an anatomical position. These results are completely independent of the approach used. LEVEL OF EVIDENCE: III Controlled cohort study.

Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine reward.

The kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression. The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. KYN levels in plasma, cerebellum, hippocampus, striatum and limbic forebrain were studied at the end of the CPP procedure. Changes in the KYN pathway after exposure to pharmacological (oxytocin and indomethacin) and environmental interventions (environmental enrichment) were also evaluated. Our results showed that defeated susceptible (SD-S) mice had higher conditioning scores than resilient mice (SD-R). In addition, although KYN concentration was elevated in all defeated mice, SD-R mice showed smaller increases in KYN concentration in the cerebellum than SD-S mice. Oxytocin or Indomethacin treatment before SD normalized cocaine-induced CPP, although the increase in the KYN pathway was maintained. However, environmental enrichment before SD normalized cocaine-induced CPP and prevented the increase in the KYN pathway. The present study highlights the role of the KYN pathway and anti-inflammatory drugs acting on TRP metabolism as pharmacological targets to potentiate resilience to social stress effects.

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice.

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body's metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice.

Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.