Sport and Recreation Related Concussion in Children: National Concussion Surveillance System.

INTRODUCTION: Concussions sustained during sports and recreational activities are a concern for young athletes. The purpose of this study was to estimate past 12-month sport- and recreation-related (SRR) traumatic brain injuries (TBIs) among a sample of children. METHODS: Pilot data from the Centers for Disease Control and Prevention's National Concussion Surveillance System were analyzed. National Concussion Surveillance System utilized a cross-sectional random-digit-dial telephone survey using computer-assisted telephone interviewing to collect self/proxy-reported data from 2018 to 2019. Adults with children aged 5-17 in the household were asked about head injuries sustained by their children. Estimates were stratified by sociodemographic and injury circumstance characteristics. Data analysis occurred from April 2022 to July 2023. RESULTS: Utilizing a tiered case definition developed by the Centers for Disease Control and Prevention, an estimated 6.9% (95% confidence interval [CI], 6.0%-7.8%) of the sample's 5-17-year-old children sustained at least one probable or possible SRR-TBI in the previous 12 months; 3.3% (95% CI, 2.7%-4.0%) of the children sustained at least one probable SRR-TBI. An estimated 63.6% (95% CI, 58.1%-69.0%) of all reported TBIs were attributed to SRR activities. Of the SRR-TBIs reported, 41.1% (95% CI, 33.0%-49.2%) were experienced while playing contact sports. Symptoms did not resolve for 8 or more days or had not resolved at the time of the interview for 18.1% (95% CI, 13.0%-23.1%) of the children's most recent SRR-TBI. CONCLUSIONS: Many proxy-reported TBIs among children aged 5-17 years were due to sports and recreational activities. Athletic trainers and healthcare providers can play a role in the prevention, identification, and management of SRR-TBIs in their respective environments.

Nonfatal Emergency Department Visits Associated with Fall-Related Fractured Skulls of Infants Aged 0-4 Months.

BACKGROUND: Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall. OBJECTIVE: This study examined caregiver actions and products associated with ED visits for fall-related fractured skulls in infants aged 0-4 months. METHODS: Data were analyzed from the 2001-2017 National Electronic Injury Surveillance System-All Injury Program. Case narratives of infants aged 0-4 months who visited an ED for a fall-related skull fracture were examined to code caregiver actions preceding the fall. Product codes determined fall location and product type involved (e.g., flooring, bed, or stairs). All national estimates were weighted. RESULTS: There were more than 27,000 ED visits (weighted estimate) of infants aged 0-4 months for a nonfatal fall-related fractured skull between 2001 and 2017. Most were younger than 2 months (46.7%) and male (54.4%). Falls occurred primarily in the home (69.9%) and required hospitalization (76.4%). Primary caregiver actions coded involved placing (58.6%), dropping (22.7%), and carrying an infant (16.6%). Floor surfaces were the most common product (mentioned in 24.0% of the cases). CONCLUSIONS: Fall-related fractured skulls are a health and developmental concern for infants, highlighting the importance of a comprehensive assessment at the time of the injury to better understand adult actions. Findings indicated the need to develop prevention messages that include safe carrying and placement of infants.

Association between traumatic brain injury and suicidality using a mediation approach and MarketScan.

INTRODUCTION: Negative outcomes, including suicidal ideation/attempts, are a major public health concern, particularly among individuals who sustain a traumatic brain injury (TBI). TBI is associated with high rates of postinjury substance use, psychiatric disorders, post-traumatic stress disorder and sleep disturbances. This study examines the mediation effects of substance use, psychiatric disorder and sleep disorder on the associations between TBI and suicidal ideation/attempts. METHODS: A matched case-control study using data from MarketScan databases for private health insurance and Medicaid from October 2015 to December 2018 estimated the association between TBI and suicidal ideation/attempts using a mediation approach. Individuals less than 65 years of age were included. RESULTS: In the Medicaid sample, psychiatric disorders mediated 22.4% of the total effect between TBI and suicidal ideation/attempt, while substance use disorders other than opioid use disorder mediated 7.47%. In the private health insurance sample, psychiatric disorders mediated 3.97% of the total effect, opioid use disorders mediated 2.08% of the total effect and sleep disorder mediated 1.25% of the total effect. CONCLUSIONS: Mediators explained less than 30% of the relationship between TBI and suicidal ideation/attempt. Findings reinforce the importance of primary prevention of TBI and monitoring patients with a TBI for risk of suicide in the first 6-12 months following injury.

Disparities in traumatic brain injury-related deaths-United States, 2020.

INTRODUCTION: Traumatic brain injury (TBI) affects how the brain functions and remains a prominent cause of death in the United States. Although preventable, anyone can experience a TBI and epidemiological research suggests some groups have worse health outcomes following the injury. METHODS: We analyzed 2020 multiple-cause-of-death data from the National Vital Statistics System to describe TBI mortality by geography, sociodemographic characteristics, mechanism of injury (MOI), and injury intent. Deaths were included if they listed an injury International Classification of Diseases, Tenth Revision (ICD-10) underlying cause of death code and a TBI-related ICD-10 code in one of the multiple-cause-of-death fields. RESULTS: During 2020, 64,362 TBI-related deaths occurred and age-adjusted rates, per 100,000 population, were highest among persons residing in the South (20.2). Older adults (≥75) displayed the highest number and rate of TBI-related deaths compared with other age groups and unintentional falls and suicide were the leading external causes among this older age group. The age-adjusted rate of TBI-related deaths in males was more than three times the rate of females (28.3 versus 8.4, respectively); further, males displayed higher numbers and age-adjusted rates compared with females for all the principal MOIs that contributed to a TBI-related death. American Indian or Alaska Native, Non-Hispanic (AI/AN) persons had the highest age-adjusted rate (29.0) of TBI-related deaths when compared with other racial and ethnic groups. Suicide was the leading external cause of injury contributing to a TBI-related death among AI/AN persons. PRACTICAL APPLICATION: Prevention efforts targeting older adult falls and suicide are warranted to reduce disparities in TBI mortality among older adults and AI/AN persons. Effective strategies are described in CDC's Stopping Elderly Accidents, Deaths, & Injuries (STEADI) initiative to reduce older adult falls and CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices for the best available evidence in suicide prevention.

Incidence of Nonfatal Traumatic Brain Injury-Related Hospitalizations - United States, 2018.

Traumatic brain injury (TBI), which can disrupt normal brain function and result in short- and long-term adverse clinical outcomes, including disability and death, is preventable. To describe the 2018 incidence of nonfatal TBI-related hospitalizations in the United States by sociodemographic characteristics, injury intent, and mechanism of injury, CDC analyzed data from the Healthcare Cost and Utilization Project (HCUP) National (Nationwide) Inpatient Sample. During 2018, there were 223,050 nonfatal TBI-related hospitalizations; rates among persons aged ≥75 years were approximately three times higher than those among persons aged 65-74 years, and the age-adjusted rate among males was approximately double that among females. Unintentional falls were the most common mechanism of injury leading to nonfatal TBI-related hospitalization, followed by motor vehicle crashes. Proper and consistent use of recommended restraints (i.e., seatbelts, car seats, and booster seats) and, particularly for persons aged ≥75 years, learning about individual fall risk from health care providers are two steps the public can take to prevent the most common injuries leading to nonfatal TBIs. The findings in this report could be used by public health officials and clinicians to identify priority areas for prevention programs.

Reported History of Traumatic Brain Injury Among Suicide Decedents: National Violent Death Reporting System, 2003-2017.

INTRODUCTION: Traumatic brain injury is a major cause of death and disability in the U.S., and research shows that individuals who suffer traumatic brain injury have an increased risk for suicide. This study examines the characteristics of suicide decedents with a documented traumatic brain injury history using a database containing circumstantial data on suicides and examines the differences in traumatic brain injury‒ and nontraumatic brain injury‒related suicides within the general population and within individuals with a history of military service. METHODS: Logistic regression models estimated AORs and 95% CIs of suicide among those with and without a previous traumatic brain injury using data from the 2003-2017 National Violent Death Reporting System (analyzed in 2020). RESULTS: From 2003 to 2017, a total of 203,157 suicide decedents were identified, and 993 had a documented traumatic brain injury before suicide. Among those with a documented traumatic brain injury, a higher percentage were White non-Hispanic. Firearm injuries were the most common method of suicide for both groups. Poisoning was more common among decedents with a previous traumatic brain injury than among those without. Male individuals, those who were single, and those who served in the military were 1.4 times more likely to have a documented traumatic brain injury history before the suicide. Almost 1 in 5 suicides (18.9%) documenting traumatic brain injury occurred among individuals with a history of military service. CONCLUSIONS: Comprehensive suicide prevention approaches are imperative. Healthcare providers can play a role in assessing and identifying patients at increased risk of suicide, including those who have experienced falls or injuries that often result in traumatic brain injury, and provide tailored interventions or referrals.

Traumatic Brain Injury-Related Emergency Department Visits Among American Indian and Alaska Native Persons-National Patient Information Reporting System, 2005-2014.

OBJECTIVE: The American Indian/Alaska Native (AI/AN) population has a disproportionately high rate of traumatic brain injuries (TBIs). However, there is little known about incidence and common mechanisms of injury among AI/AN persons who seek care in an Indian Health Service (IHS) or tribally managed facility. METHODS: Using the IHS National Patient Information Reporting System, we assessed the incidence of TBI-related emergency department visits among AI/AN children and adults seen in IHS or tribally managed facilities over a 10-year period (2005-2014). RESULTS: There were 44 918 TBI-related emergency department visits during the study period. Males and persons aged 18 to 34 years and 75 years and older had the highest rates of TBI-related emergency department visits. Unintentional falls and assaults contributed to the highest number and proportion of TBI-related emergency department visits. The number and age-adjusted rate of emergency department visits for TBI were highest among persons living in the Southwest and Northern Plains when compared with other IHS regions. CONCLUSION: Thousands of AI/AN children and adults are seen each year in emergency departments for TBI and the numbers increased over the 10-year period examined. Evidence-based interventions to prevent TBI-related emergency department visits, such as programs to reduce the risk for older adult falls and assault, are warranted.

Deaths from Fall-Related Traumatic Brain Injury - United States, 2008-2017.

One in 10 U.S. residents aged ≥18 years reports falling each year (1). Among all age groups, falls can cause serious injury and are the second leading cause of traumatic brain injury (TBI)-related deaths (2). TBI is a head injury caused by a bump, blow, or jolt to the head or body or a penetrating head injury that results in disruption of normal brain function.* CDC estimated national and state-specific rates and trends for TBI-related deaths (TBI deaths) caused by unintentional falls (fall-related TBI deaths) among U.S. residents during 2008-2017, by selected decedent characteristics. The national age-adjusted rate of fall-related TBI deaths increased by 17% from 2008 to 2017. Rate trends at the national level increased significantly for nearly all decedent characteristics, with the most notable increases observed among persons living in noncore (i.e., most rural), nonmetropolitan counties and those aged ≥75 years. Analysis of state-specific rate trends determined that rates of fall-related TBI deaths increased significantly in 29 states over the 10-year study period. A fall can happen to anyone of any age, but falls are preventable. Health care providers and the public need to be aware of evidence-based strategies to prevent falls, given that rates of fall-related TBI deaths are increasing. Health care providers can educate patients on fall and TBI prevention, assess their risk for falls, and when needed, encourage participation in appropriate evidence-based fall prevention programs.†.

Traumatic brain injury-related hospitalizations and deaths among American Indians and Alaska natives - United States, 2008-2014.

INTRODUCTION: Despite progress, injury remains the leading cause of preventable death for American Indian and Alaska Natives (AI/AN), aged 1 to 44. There are few publications on injuries among the AI/AN population, especially those on traumatic brain injury (TBI). A TBI can cause short- or long-term changes in cognition, communication, and/or emotion. METHODS: To describe changes over time in TBI incidence by mechanism of injury, injury intent, and age group among AI/ANs, the CDC analyzed hospitalization and death data from the 2008-2014 Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) and the National Vital Statistics System (NVSS), respectively. RESULTS: From 2008-2014, the incidence of TBI-related hospitalizations increased by 32% (1,477 in 2008 to 1,945 in 2014) and resulted in a 21% increase in age-adjusted rates of people hospitalized with TBI. TBI-related deaths increased in number (569 in 2008 to 644 in 2014) and age-adjusted rate (22.7 in 2008 to 25.4 in 2014) by approximately 13% and 12%, respectively. Motor-vehicle crashes were the leading cause of TBI-related deaths among AI/ANs aged 0-54 years. Practical application: Prevention efforts should focus on increasing motor-vehicle safety and advancing prevention strategies for other leading causes of TBI, including: falls, intentional self-harm, and assaults.

Evaluation of a hospital-based injury surveillance system for monitoring road traffic deaths in Phuket, Thailand.

Objectives: The objective of this study was to evaluate and injury surveillance (IS) system's ability to monitor road traffic deaths and the coverage of road traffic injury and death surveillance in Phuket, Thailand. Methods: U.S. Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to qualitatively and quantitatively evaluate IS. Interviews with key stakeholders focused on IS's usefulness, simplicity, flexibility, acceptability, and stability. Active case finding of 2014 road traffic deaths in all paper and electronic hospital record systems was used to assess system sensitivity, positive predictive value, and data quality. Electronic data matching software was used to determine the implications of combining IS data with other provincial-level data sources (e.g., death certificates, electronic vehicle insurance claim system). Results: Evaluation results indicated that IS was useful, flexible, acceptable, and stable, with a high positive predictive value (99%). Simplicity was limited due to the burden of collecting data on all injuries and use of paper-based data collection forms. Sensitivity was low, with IS only identifying 55% of hospital road traffic death cases identified during active case finding; however, IS cases were representative of cases identified. Data accuracy and completeness varied across data fields. Combining IS with active case finding, death certificates, and the electronic vehicle insurance claim system more than doubled the number of road traffic death cases identified in Phuket. Conclusion: An efficient and comprehensive road traffic injury and death surveillance system is critical for monitoring Phuket's road traffic burden. The hospital-based IS system is a useful system for monitoring road traffic deaths and assessing risk behaviors. However, the complexity of data collection and limited coverage hinders the ability of IS to fully represent road traffic deaths in Phuket Province. Combining data sources could improve coverage and should be considered.

Emergency Department Visits for Sports- and Recreation-Related Traumatic Brain Injuries Among Children - United States, 2010-2016.

Traumatic brain injuries (TBIs), including concussions, are at the forefront of public concern about athletic injuries sustained by children. Caused by an impact to the head or body, a TBI can lead to emotional, physiologic, and cognitive sequelae in children (1). Physiologic factors (such as a child's developing nervous system and thinner cranial bones) might place children at increased risk for TBI (2,3). A previous study demonstrated that 70% of emergency department (ED) visits for sports- and recreation-related TBIs (SRR-TBIs) were among children (4). Because surveillance data can help develop prevention efforts, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP)* by examining SRR-TBI ED visits during 2010-2016. An average of 283,000 children aged <18 years sought care in EDs each year for SRR-TBIs, with overall rates leveling off in recent years. The highest rates were among males and children aged 10-14 and 15-17 years. TBIs sustained in contact sports accounted for approximately 45% of all SRR-TBI ED visits. Activities associated with the highest number of ED visits were football, bicycling, basketball, playground activities, and soccer. Limiting player-to-player contact and rule changes that reduce risk for collisions are critical to preventing TBI in contact and limited-contact sports. If a TBI does occur, effective diagnosis and management can promote positive health outcomes among children.

Exploring substance use and impaired driving among adults aged 21 years and older in the United States, 2015.

INTRODUCTION: Alcohol- or drug-impaired driving can cause motor vehicle crashes, injuries, and death. Estimates of drug-impaired driving are difficult to obtain. This study explores self-reported prevalence of and factors associated with alcohol, marijuana, and prescription opioid use and impaired driving among adults aged 21 years and older in the United States. METHODS: Self-reported data from 3,383 adults in the 2015 Fall ConsumerStyles survey were analyzed. Respondents were asked about alcohol, marijuana, and prescription opioid use and driving while impaired in the last 30 days. Weighted prevalence estimates were calculated. Prevalence ratios and Poisson log-linear regressions were used to identify factors associated with substance use and impaired driving. RESULTS: Alcohol use was reported by 49.5% (n = 1,676) of respondents; of these, 4.9% (n = 82) reported alcohol-impaired driving. Marijuana use was reported by 5.5% (n = 187) of respondents; of these, 31.6% (n = 59) reported marijuana-impaired driving. Prescription opioid use was reported by 8.8% (n = 298) of respondents; of these, 3.4% (n = 10) reported prescription opioid-impaired driving. Polysubstance use of alcohol and marijuana (concurrent use) was reported by 2.7% (n = 93) of respondents. Among those, 10.8% (n = 10) reported driving impaired by both alcohol and marijuana. CONCLUSIONS: Impaired driving was self-reported among alcohol, marijuana, and prescription opioid users. This article demonstrates the need for more robust alcohol- and drug-related data collection, reporting, and analyses, as well as the emerging need for surveillance of marijuana and prescription opioid-impaired driving. States can consider using proven strategies to prevent impaired driving and evaluate promising practices.

Self-Reported Concussions from Playing a Sport or Being Physically Active Among High School Students - United States, 2017.

Increased susceptibility to concussions and longer recovery times among high school athletes compared with older athletes (1) make concussions among youths playing a sport or being physically active an area of concern. Short-term and long-term sequelae of concussions can include cognitive, affective, and behavioral changes (1). Surveillance methods used to monitor concussions among youths likely underestimate the prevalence. Estimates assessed from emergency departments miss concussions treated outside hospitals, those generated using high school athletic trainer reports miss concussions sustained outside of school-based sports (2), and both sources miss medically untreated concussions. To estimate the prevalence of concussions among U.S. high school students related to playing a sport or being physically active, CDC analyzed data from the 2017 national Youth Risk Behavior Survey (YRBS). Overall, 15.1% of students (approximately 2.5 million*) reported having at least one of these concussions during the 12 months before the survey, and 6.0% reported two or more concussions. Concussion prevalence was significantly higher among male students than among female students and among students who played on a sports team than among students who did not. Among all sex, grade, and racial/ethnic subgroups, the odds of reporting a concussion increased significantly with the number of sports teams on which students played. These findings underscore the need to 1) foster a culture of safety in which concussion prevention and management is explicitly addressed; 2) expand efforts to educate students, parents, coaches, and health care providers regarding the risk for concussion; and 3) identify programs, policies, and practices that prevent concussions.

Ability to monitor driving under the influence of marijuana among non-fatal motor-vehicle crashes: An evaluation of the Colorado electronic accident reporting system.

INTRODUCTION: As more states legalize medical/recreational marijuana use, it is important to determine if state motor-vehicle surveillance systems can effectively monitor and track driving under the influence (DUI) of marijuana. This study assessed Colorado's Department of Revenue motor-vehicle crash data system, Electronic Accident Reporting System (EARS), to monitor non-fatal crashes involving driving under the influence (DUI) of marijuana. METHODS: Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to assess EARS' usefulness, flexibility, timeliness, simplicity, acceptability, and data quality. We assessed system components, interviewed key stakeholders, and analyzed completeness of Colorado statewide 2014 motor-vehicle crash records. RESULTS: EARS contains timely and complete data, but does not effectively monitor non-fatal motor-vehicle crashes related to DUI of marijuana. Information on biological sample type collected from drivers and toxicology results were not recorded into EARS; however, EARS is a flexible system that can incorporate new data without increasing surveillance system burden. CONCLUSIONS: States, including Colorado, could consider standardization of drug testing and mandatory reporting policies for drivers involved in motor-vehicle crashes and proactively address the narrow window of time for sample collection to improve DUI of marijuana surveillance. Practical applications: The evaluation of state motor-vehicle crash systems' ability to capture crashes involving drug impaired driving (DUID) is a critical first step for identifying frequency and risk factors for crashes related to DUID.

Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

Dose-dependent effectiveness of wheel running to attenuate cocaine-seeking: impact of sex and estrous cycle in rats.

RATIONALE: Exercise has shown promise as an intervention for drug addiction; however, little is known regarding the exercise conditions that most effectively reduce relapse vulnerability and whether these conditions differ by sex. OBJECTIVE: Here, we examined sex differences in the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking. METHODS: Male and female rats self-administered cocaine (1.5 mg/kg/infusion) under extended access conditions (24 h/day, 4 discrete trials/h) for 10 days. Rats were then given voluntary access to either an unlocked or locked running wheel for 1, 2, 6, or 24 h/day during the 14-day abstinence period. Separate groups of rats were housed in polycarbonate cages during abstinence to control for physical activity that the wheel may provide. Subsequent cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure. Estrous cycle was monitored in females to determine whether the effectiveness of wheel running varied by estrous cycle phase. RESULTS: Although females ran more than males, males were more sensitive to the effects of running and showed a dose-dependent decrease in cocaine-seeking with longer access resulting in greater suppression. The dose-effect relationship was less straightforward in females and access to both a locked and unlocked wheel decreased cocaine-seeking with effects dependent on estrous cycle phase. Notably, extended (6 and 24 h/day), but not limited (1 and 2 h/day) access to a wheel surmounted the heightened vulnerability observed in females during estrus. CONCLUSION: Taken together, our findings suggest that the effectiveness of wheel running is dose-, sex-, and estrous cycle-dependent.

Dose-dependent effects of wheel running on cocaine-seeking and prefrontal cortex Bdnf exon IV expression in rats.

RATIONALE: Physical activity, and specifically exercise, has shown promise as an intervention for drug addiction; however, the exercise conditions that produce the most efficacious response, as well as its underlying mechanism, are unknown. OBJECTIVE: In this study, we examined the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking and associated changes in prefrontal cortex (PFC) brain-derived neurotrophic factor (Bdnf) exon IV expression, a marker of epigenetic regulation implicated in cocaine relapse and known to be regulated by exercise. METHODS: Cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure following extended access cocaine or saline self-administration (24-h/day, 4 discrete trials/h, 10 days, 1.5 mg/kg/infusion) and a 14-day abstinence period. During abstinence, rats had either locked or unlocked running wheel access for 1, 2, or 6 h/day. Bdnf exon IV expression was assessed using quantitative real-time polymerase chain reaction. RESULTS: Cocaine-seeking was highest under the locked wheel condition, and wheel running dose dependently attenuated this effect. Cocaine increased Bdnf exon IV expression, and wheel running dose dependently attenuated this increase, with complete blockade in rats given 6-h/day access. Notably, the efficacy of exercise was inversely associated with Bdnf exon IV expression, and both its efficacy and its effects on Bdnf exon IV expression were mimicked by treatment during abstinence with sodium butyrate, a histone deacetylase inhibitor that, like exercise, modulates gene transcription, including Bdnf exon IV expression. CONCLUSION: Taken together, these results indicate that the efficacy of exercise is dose dependent and likely mediated through epigenetic regulation of PFC Bdnf.

Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis.

Physical activity, and specifically exercise, has been suggested as a potential treatment for drug addiction. In this review, we discuss clinical and preclinical evidence for the efficacy of exercise at different phases of the addiction process. Potential neurobiological mechanisms are also discussed focusing on interactions with dopaminergic and glutamatergic signaling and chromatin remodeling in the reward pathway. While exercise generally produces an efficacious response, certain exercise conditions may be either ineffective or lead to detrimental effects depending on the level/type/timing of exercise exposure, the stage of addiction, the drug involved, and the subject population. During drug use initiation and withdrawal, its efficacy may be related to its ability to facilitate dopaminergic transmission, and once addiction develops, its efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. We conclude with future directions, including the development of exercise-based interventions alone or as an adjunct to other strategies for treating drug addiction.

Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

BACKGROUND: Exercise has recently been suggested as an attractive alternative to pharmacotherapy for treating drug addiction. The goal of this study was to determine, using an animal model, whether aerobic exercise may block reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal signaling in the prefrontal cortex). METHODS: Following acquisition and 10 days of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete trial procedure (four infusions/hr), rats began a 14-day abstinence period. During this period, rats were either given access to a running-wheel for 2-hours each day or placed in similar boxes with the wheel locked. Cocaine-seeking was assessed following the 14th day of abstinence using a within-session extinction/cue-induced reinstatement procedure. Neuronal activity was assessed by examining phosphorylated levels of extracellular signal-regulated kinase (pERK) using Western blot analysis. RESULTS: Wheel running reduced cocaine-seeking during both extinction and reinstatement. Cocaine-seeking was positively associated with pERK levels in the prefrontal cortex. Although pERK levels were not different among saline controls, in the cocaine group, pERK levels were significantly decreased by exercise. CONCLUSIONS: Aerobic exercise may reduce relapse vulnerability by preventing the increase in cocaine-seeking and associated neuroadaptations in the prefrontal cortex that develop over an abstinence period.