Empirical Derivation and Prediction of Treatment Trajectories in Harmonized AUD Clinical Trial Datasets.

In clinical settings targeting alcohol use disorder (AUD), it is often unclear whether a treatment option may best suit a patient's clinical needs. Clinicians providing AUD treatment are often required to predict patients' responses to guide treatment decisions. Recently, machine learning approaches have been used as tools in precision medicine to help guide these clinical decisions.

Multidimensional components of impulsivity during early adolescence: Relationships with brain networks and future substance-use in the Adolescent Brian and Cognitive Development (ABCD) study.

Impulsivity is a multifaceted construct that typically increases during adolescence and is implicated in risk for substance use disorders that develop later in life. Here, we take a multivariate approach to identify latent dimensions of impulsivity, broadly defined, among youth enrolled in the Adolescent Brain and Cognitive Development (ABCD) study and explore associations with individual differences in demographics, substance-use initiation and canonical resting state networks (N=11,872, ages ~9-10). Using principal component analysis, we identified eight latent impulsivity dimensions, the top three of which together accounted for the majority of the variance across all impulsivity assessments.

Cocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder.

Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments. Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions.

Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study.

Adolescence is the peak period for the emergence of substance use, which can lead to long-term psychosocial, occupational and interpersonal complications. Ongoing large-scale, longitudinal, consortium initiatives, such as the Adolescent Brain and Cognitive Development (ABCD) study, offer unprecedented opportunities to elucidate key risk factors for problematic substance use in a well-powered sample and to examine how changes in risk factors relate to symptoms across time. Delay discounting has been proposed as a putative risk marker for early substance-use initiation and other forms of psychopathology.

Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities.

Importance: The experienced consequences of the COVID-19 pandemic have diverged across individuals, families, and communities, resulting in inequity within a host of factors. There is a gap of quantitative evidence about the transgenerational impacts of these experiences and factors.

Objective: To identify baseline predictors of COVID-19 experiences, as defined by child and parent report, using a multivariate pattern-learning framework from the Adolescent Brain and Cognitive Development (ABCD) cohort.

Combined effects of mephedrone and cocaine on locomotor activity and conditioned place preference in male Sprague-Dawley rats.

Mephedrone (MEPH) is one of several synthetic cathinone derivatives and a common constituent of illicit 'bath salts'. Concomitant use of MEPH with other psychostimulants is common among recreational users, but their combined effects have not been evaluated rigorously. In experiment 1, 56 male Sprague-Dawley rats were administered saline, MEPH (1 or 5 mg/kg), COC (5 mg/kg), or a mixture of MEPH (1 or 5 mg/kg) + COC (5 mg/kg) for seven consecutive days.

Repeated exposure to 3,4-methylenedioxypyrovalerone and cocaine produces locomotor sensitization with minimal effects on brain monoamines.

Synthetic cathinones, known as "bath salts" on the illicit drug market, pose a significant public health concern. 3,4-Methylenedioxypyrovalerone (MDPV), one of several popular constituents of illicit bath salts, produces similar pharmacological actions to cocaine, albeit with greater potency and efficacy. The present study sought to characterize behavioral and neurochemical effects of repeated exposure to MDPV alone and in combination with cocaine.

Differences in hippocampal serotonergic activity in a mouse single prolonged stress paradigm impact discriminant fear acquisition and retention.

A mouse model of traumatic stress provided insight into a mechanism of individual differences in conditioned fear responding. Hippocampal serotonergic activity (metabolic turnover) was associated with increased behavioral freezing during fear acquisition in a portion of trauma-exposed subjects. These subjects later displayed enhanced fear to the neutral cue during retention.

Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD.

Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC).

Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.

A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug-able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2-day drug-free period.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS.