Anxiety and risk-taking behavior maps onto opioid and alcohol polysubstance consumption patterns in male and female mice.

Polysubstance use is prevalent in the population but remains understudied in preclinical models. Alcohol and opioid polysubstance use is associated with negative outcomes, worse treatment prognosis, and higher overdose risk; but underlying mechanisms are still being uncovered. Examining factors that motivate use of one substance over another in different contexts in preclinical models will better our understanding of polysubstance use and improve translational value. Here we assessed baseline anxiety-like and locomotive behavior and then measured voluntary consumption of multiple doses of alcohol and fentanyl in group housed male and female mice using our novel Socially Integrated Polysubstance (SIP) system. Fifty-six male (n=32) and female (n=24) adult mice were housed in groups of 4 for one week with continuous access to food, water, two doses of ethanol (5% and 10%) and two doses of fentanyl (5 ug/ml and 20 ug/ml). Our analyses revealed sex differences across multiple domains - female mice consumed more liquid in the dark cycle, had higher activity, a higher preference for both ethanol and fentanyl over water, and their fentanyl preference increased over the seven days. We then used machine-learning techniques to reveal underlying relationships between baseline behavioral phenotypes and subsequent polysubstance consumption patterns, where anxiety-and risk-taking-like behavioral phenotypes mapped onto discrete patterns of polysubstance use, preference, and escalation. By simulating more translationally relevant substance use and improving our understanding of the motivations for different patterns of consumption, this study contributes to the developing preclinical literature on polysubstance use with the goal of facilitating better treatment outcomes and novel therapeutic strategies.

Socially Integrated Polysubstance (SIP) system: An open-source solution for continuous monitoring of polysubstance fluid intake in group housed mice.

Despite impressive results from neuroscience research using rodent models, there is a paucity of successful translation from preclinical findings to effective pharmacological interventions for treatment of substance use disorder (SUD) in humans. One potential reason for lack of translation from animal models is difficulty in accurately replicating the lived experience of people who use drugs. Aspects of substance use in humans that are often not modeled in animal research include but are not limited to 1) voluntary timing and frequency of substance intake, 2) social environment during substance use, and 3) access to multiple substances and multiple concentrations of each substance. Critically, existing commercial equipment that allows for social housing and voluntary polysubstance use (e.g., home cage monitoring system) is prohibitively expensive and no open-source solutions exist. With these goals in mind, here we detail development of the Socially Integrated Polysubstance (SIP) system, an open-source and lower cost solution that allows for group housed rodents to self-administer multiple substances with continuous monitoring and measurement. In our current setup, each SIP cage contains four drinking stations, and each station is equipped with a RFID sensor and sipper tube connected to a unique fluid reservoir. Using this system, we can track which animal (implanted with unique RFID transponder) visits which drinking location and the amount they drink during each visit (in 20 ul increments). Using four flavors of Kool-Aid, here we demonstrate that the SIP system is reliable and accurate with high temporal resolution for long term monitoring of substance intake and behavior tracking in a social environment. The SIP cage system is a first step towards designing an accessible and flexible rodent model of substance use that more closely resembles the experience of people who use drugs.

Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice.

Blast exposure (via detonation of high explosives) represents a major potential trauma source for Servicemembers and Veterans, often resulting in mild traumatic brain injury (mTBI). Executive dysfunction (e.g., alterations in memory, deficits in mental flexibility, difficulty with adaptability) is commonly reported by Veterans with a history of blast-related mTBI, leading to impaired daily functioning and decreased quality of life, but underlying mechanisms are not fully understood and have not been well studied in animal models of blast. To investigate potential underlying behavioral mechanisms contributing to deficits in executive functioning post-blast mTBI, here we examined how a history of repetitive blast exposure in male mice affects anxiety/compulsivity-like outcomes and appetitive goal-directed behavior using an established mouse model of blast mTBI. We hypothesized that repetitive blast exposure in male mice would result in anxiety/compulsivity-like outcomes and corresponding performance deficits in operant-based reward learning and behavioral flexibility paradigms. Instead, results demonstrate an increase in reward-seeking and goal-directed behavior and a congruent decrease in behavioral flexibility. We also report chronic adverse behavioral changes related to anxiety, compulsivity, and hyperarousal. In combination, these data suggest that potential deficits in executive function following blast mTBI are at least in part related to enhanced compulsivity/hyperreactivity and behavioral inflexibility and not simply due to a lack of motivation or inability to acquire task parameters, with important implications for subsequent diagnosis and treatment management.

The challenges of providing eye care for adults with intellectual disabilities.

This review is intended to raise awareness of the importance of providing high-quality eye care for people with intellectual disabilities and the increasing need for this eye care to be community-based. We describe the challenges to the provision of high-quality community-based eye care for people with intellectual disabilities and ideas, evidence and methods for overcoming them. The prevalence of visual impairment in people with intellectual disabilities has been reported to be at least 40 per cent, rising to as high as 100 per cent in those with profound and severe disabilities. A progressive move toward deinstitutionalisation has shifted the provision of care for people with intellectual disabilities. Individuals can have the freedom to access health-care services of their choice. This has posed challenges to the health-care system, including how to deliver high-quality community-based eye care, creating a current significant unmet need for eye-care services. Undiagnosed refractive error and under-prescription of spectacles are major reasons for avoidable visual impairment among people with disabilities. There is an apparent reluctance of optometrists to engage in this work due to the perceived difficulties of working with people with intellectual and multiple disabilities. There are challenges associated with diagnosis and management of ocular conditions in people with intellectual disabilities and the demand is clear. Small shifts in training, knowledge and awareness would place optometry well to meet the challenges of this specialised area of eye care.