Pain in alcohol use disorder: Evaluating effects of childhood trauma, perceived stress, and psychological comorbidity.

The relationship between pain and alcohol use disorder (AUD) is complex and bidirectional. The current study examines risk factors for pain in a large comprehensively phenotyped sample including individuals from across the spectrum of alcohol use and misuse. Participants (n = 1101) were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and included treatment-seeking AUD inpatients (AUD+Tx, n = 369), individuals with AUD not seeking treatment (AUD+, n = 161), and individuals without AUD (AUD-, n = 571).

Scaling eukaryotic cell-free protein synthesis achieved with the versatile and high-yielding tobacco BY-2 cell lysate.

Eukaryotic cell-free protein synthesis (CFPS) can accelerate expression and high-throughput analysis of complex proteins with functionally relevant post-translational modifications (PTMs). However, low yields and difficulties scaling such systems have prevented their widespread adoption in protein research and manufacturing. Here, we provide detailed demonstrations for the capabilities of a CFPS system derived from Nicotiana tabacum BY-2 cell culture (BY-2 lysate; BYL).

An update on the assessment of culture and environment in the ABCD Study®: Emerging literature and protocol updates over three measurement waves.

Advances in our understanding of risk and resilience factors in adolescent brain health and development increasingly demand a broad set of assessment tools that consider a youth's peer, family, school, neighborhood, and cultural contexts in addition to neurobiological, genetic, and biomedical information. The Culture and Environment (CE) Workgroup (WG) of the Adolescent Brain Cognitive Development (ABCD) Study curates these important components of the protocol throughout ten years of planned data collection. In this report, the CE WG presents an update on the evolution of the ABCD Study® CE protocol since study inception (Zucker et al.

Thermostability of a recombinant G protein-coupled receptor expressed at high level in mammalian cell culture.

Rational design of pharmaceutical drugs targeting integral membrane G protein-coupled receptors (GPCR) requires thorough understanding of ligand binding and mechanism of activation through high resolution structural studies of purified proteins. Due to inherent conformational flexibility of GPCR, stabilization of these proteins solubilized from cell membranes into detergents is a challenging task. Here, we take advantage of naturally occurring post-translational modifications for stabilization of purified GPCR in detergent micelles.

The endocannabinoid system in the amygdala and modulation of fear.

Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and behavioral phenotype. Although many individuals that experience trauma are able to gradually diminish their emotional responding to trauma-related stimuli over time, known as extinction learning, individuals suffering from PTSD are impaired in this capacity. An inability to decline this initially normal and adaptive fear response, can be confronted with exposure-based therapies, often in combination with pharmacological treatments.

Dorsolateral striatum engagement during reversal learning.

Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS involvement in a touchscreen-based reversal task requiring mice to update choice following a change in stimulus-reward contingencies. In vivo single-unit recordings in the DLS showed reversal produced a population-level shift from excited to inhibited neuronal activity prior to choices being made.

Akinetic rigid symptoms are associated with decline in a cortical motor network in Parkinson's disease.

The akinetic/rigid (AR) motor subtype of Parkinson's Disease is associated with increased rates of motor and cognitive decline. Cross-sectional studies examining the neural correlates of AR have found abnormalities in both subcortical and cortical networks involved in motor planning and execution relative to controls. To better understand how these cross-sectional findings are implicated in the unique decline associated with the AR subtype, we examined whether baseline AR symptoms are associated with longitudinal decline of these networks, in contrast to other motor symptoms such as tremor.

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women.

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women.

Brain Network Segregation and Glucose Energy Utilization: Relevance for Age-Related Differences in Cognitive Function.

The human brain is organized into segregated networks with strong within-network connections and relatively weaker between-network connections. This "small-world" organization may be essential for maintaining an energetically efficient system, crucial to the brain which consumes 20% of the body's energy. Brain network segregation and glucose energy utilization both change throughout the lifespan.

Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice.

N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor.

Brain structural changes in cannabis dependence: association with MAGL.

Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD.

Reduced Segregation Between Cognitive and Emotional Processes in Cannabis Dependence.

Addiction is characterized by an erosion of cognitive control toward drug taking that is accentuated by negative emotional states. Here we tested the hypothesis that enhanced interference on cognitive control reflects a loss of segregation between cognition and emotion in addiction. We analyzed Human Connectome Project data from 1206 young adults, including 89 with cannabis dependence (CD).

Correction: Striato-cortical tracts predict 12-h abstinence-induced lapse in smokers.

The original version of this article contained an error in the affiliation of Dahua Yu, which was incorrectly stated as affiliation 3 (Engineering Research Center of Molecular and Neuro Imaging Ministry of Education, Xi'an Shaanxi, 710071, People's Republic of China), when this author is actually linked to affiliation 4 (Inner Mongolia Key Laboratory of Pattern Recognition and Intelligent Image Processing, School of Information Engineering, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, People's Republic of China).

Expression and Preparation of a G-Protein-Coupled Cannabinoid Receptor CB for NMR Structural Studies.

Cannabinoid receptor type II, or CB , is an integral membrane protein that belongs to a large class of G-protein-coupled receptors (GPCR)s. CB is a part of the endocannabinoid system, which plays an important role in the regulation of immune response, inflammation, and pain. Information about the structure and function of CB is essential for the development of specific ligands targeting this receptor.

A novel multichoice touchscreen paradigm for assessing cognitive flexibility in mice.

Cognitive flexibility refers to various processes which enable behaviors to be modified on the basis of a change in the contingencies between stimuli or responses and their associated outcomes. Reversal learning is a form of cognitive flexibility which measures the ability to adjust responding based on a switch in the stimulus-outcome contingencies of, typically two, perceptually distinct stimuli. Reversal tasks have provided valuable insight into the neural basis of cognitive flexibility, implicating brain regions including the lateral orbitofrontal cortex (lOFC) and dorsomedial prefrontal cortex (dmPFC).

Correction to: Internet gaming disorder: deficits in functional and structural connectivity in the ventral tegmental area-Accumbens pathway.

The original version of this article contained mistakes, and the authors would like to correct them. The correct details are given below.

Striato-cortical tracts predict 12-h abstinence-induced lapse in smokers.

Striatal circuit dysfunction is implicated in smoking behaviors and lapses during abstinence attempts. However, little is known about whether the structural connectivity of striatal tracts can be used to predict abstinence-induced craving and lapses. The tract strengths of striatal circuits were compared in 53 male nicotine-dependent cigarette smokers and 58 matched nonsmokers, using seed-based classification by diffusion tensor imaging (DTI) probabilistic tractography with 10 a priori target masks.

Abnormal frontostriatal tracts in young male tobacco smokers.

Dysfunctions in frontostriatal circuits have been associated with craving and cognitive control in smokers. However, the relevance of white matter (WM) diffusion properties of the ventral and dorsal frontostriatal tracts for behaviors associated with smoking remains relatively unknown, especially in young adulthood, a critical time period for the development and maintenance of addiction. Here, diffusion tensor imaging (DTI) and probabilistic tractography were used to investigate the WM tracts of the ventral and dorsal frontostriatal circuits in two independent studies (Study1: 36 male smokers (21.

Internet gaming disorder: deficits in functional and structural connectivity in the ventral tegmental area-Accumbens pathway.

Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and from the substantia nigra (SN) to the dorsal striatum are involved in addiction. However, relatively little is known about the implication of these circuits in Internet gaming disorder (IGD). This study examined the alteration of resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI) -based structural connectivity of VTA/SN circuits in 61 young male participants (33 IGD and 28 healthy controls).

Genome-wide association for testis weight in the diversity outbred mouse population.

Testis weight is a genetically mediated trait associated with reproductive efficiency across numerous species. We sought to evaluate the genetically diverse, highly recombinant Diversity Outbred (DO) mouse population as a tool to identify and map quantitative trait loci (QTLs) associated with testis weight. Testis weights were recorded for 502 male DO mice and the mice were genotyped on the GIGAMuga array at ~ 143,000 SNPs.

Effect of combined naltrexone and bupropion therapy on the brain's functional connectivity.

Background: The control of food intake in environments with easy access to highly rewarding foods is challenging to most modern societies. The combination of sustained release (SR) naltrexone and SR bupropion (NB32) has been used in weight-loss and obesity management. However, the effects of NB32 on the brain circuits implicated in the regulation of food intake are unknown.

Fear extinction requires infralimbic cortex projections to the basolateral amygdala.

Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role.

Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson's disease.

Dopaminergic medications improve the motor symptoms of Parkinson's disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during functional magnetic resonance imaging.

Subcortical Local Functional Hyperconnectivity in Cannabis Dependence.

Background: Cannabis abuse (CA) has been associated with psychopathology, including negative emotionality and higher risk of psychosis, particularly with early age of initiation. However, the mechanisms underlying this association are poorly understood. Because aberrant dopamine signaling is implicated in cannabis-associated psychopathology, we hypothesized that regular CA would be associated with altered resting-state functional connectivity in dopamine midbrain-striatal circuits.