Breaking News
August 21, 2018 - National Foundation for Cancer Research receives Safeway Foundation grant
August 21, 2018 - Protein aggregation in neurons linked to gene regulation in Huntington’s disease
August 21, 2018 - Aravive Biologics gains Fast Track Designation for AVB-S6-500 from U.S. FDA
August 21, 2018 - FDA Approves Opdivo (nivolumab) for Certain Patients with Previously Treated Small Cell Lung Cancer
August 21, 2018 - Success of blood test for autism affirmed
August 21, 2018 - Diabetic patients with disrupted sleep may need more time to heal their wounds
August 21, 2018 - AADE honors six educators for achievements in diabetes education
August 21, 2018 - Scientists find two molecules that may combat cancer and chronic infections
August 21, 2018 - Two Strategies for Preventing Diabetes in Minority Patients
August 21, 2018 - Living as a Gallbladder Cancer Survivor
August 21, 2018 - Can we predict the long-term outcome of boys with ADHD?
August 21, 2018 - GBCA creates model for developing scientist-advocate collaborations in cancer research
August 21, 2018 - Healthy diet could help promote healthy cellular aging in women
August 21, 2018 - Researchers develop gene expression predictor for immunotherapy response in melanoma
August 21, 2018 - MDI Biological Laboratory introduces Morris Scientific Discovery Fund for eligible research programs
August 21, 2018 - Micro-flow model reveals complex interactions between the brain’s blood vessels and nerve cells
August 21, 2018 - Study investigates impact of osteoporosis on risk of developing dementia
August 21, 2018 - Federal method fails to detect most stores that sell cigarettes to minors
August 21, 2018 - Workers in open office seating have less stress than those in private offices and cubicles
August 21, 2018 - 1 in 4 in U.S. Has a Disability, CDC Reports
August 21, 2018 - Studies provide new insights into the role of sleep in chronic pain
August 21, 2018 - Study shows that rogue proteins may underlie some ALS and frontotemporal dementia cases
August 21, 2018 - Elevated LDL cholesterol levels linked to higher risk of CVD death in young, healthy people
August 21, 2018 - Measles cases on the rise in Europe
August 21, 2018 - CURE Media Group welcomes CancerCare to Strategic Alliance Partnership Program
August 21, 2018 - Blood management program associated with fewer transfusions in orthopedic patients
August 21, 2018 - Researchers create the world’s first artificial retina
August 21, 2018 - Yale researchers identify racial disparities in prescribing opioids for chronic pain
August 21, 2018 - BOOST-3 clinical trial aims to improve outcomes for severe TBI patients
August 21, 2018 - New study highlights Alzheimer’s herpes link, experts say
August 21, 2018 - Airline crew don’t have significantly elevated risk of thyroid cancer, new study finds
August 21, 2018 - States leverage federal funds to help insurers lower premiums
August 21, 2018 - New badge course explores research around skeletal muscle as an endocrine organ
August 21, 2018 - TG Therapeutics Announces Completion of Target Enrollment in the ULTIMATE Phase 3 Trials in Multiple Sclerosis
August 21, 2018 - Increased levels of human herpesvirus ID’d in Alzheimer’s
August 21, 2018 - To help patients quash pain, researcher develops practical guide for health care providers
August 20, 2018 - Medicine on the front line to be presented at Medical Innovation 2018
August 20, 2018 - Harbour Biomed and Kelun-Biotech collaborate to develop, commercialize anti-PD-L1 antibody
August 20, 2018 - The man who sold America on vitamin D — and profited in the process
August 20, 2018 - Finding the light in antimicrobials
August 20, 2018 - Unique pain program helps surgical patients wean off opioids safely and effectively
August 20, 2018 - Strawberries could mitigate colonic inflammation
August 20, 2018 - FDA Accepts New Drug Application (NDA) to Review Midazolam Nasal Spray, an Investigational Product for the Acute Treatment of Seizure Clusters
August 20, 2018 - Using Facebook to help young adults quit smoking
August 20, 2018 - ‘Liquid biopsy’ predicts lymphoma therapy success within days | News Center
August 20, 2018 - 5 Questions with Jordan Orange, Chair of Pediatrics
August 20, 2018 - New assay may help improve both sarcoma diagnosis and treatment
August 20, 2018 - New information on the brain regions related to metacognition, tactile sense
August 20, 2018 - New class of insect repellents to fight against mosquito-borne diseases
August 20, 2018 - ACA Coverage Gains Include Workers Without Insurance
August 20, 2018 - 3-D printed biomaterials for bone tissue engineering
August 20, 2018 - Current surveillance system does not quickly pick up most listeriosis cases in the EU, study reveals
August 20, 2018 - Prenatal exposure to acute stress can affect cognitive function in children of low-income households
August 20, 2018 - New study examines scope of state policies targeting drug use by pregnant women
August 20, 2018 - Researchers find long-term structural, functional brain abnormalities in individuals with AUDs
August 20, 2018 - Shortage of insurance fraud cops sparks campaign debate
August 20, 2018 - Researchers find STAT3 as therapeutic target for chronic active EBV infection
August 20, 2018 - Health Tip: Keep Diabetic Feet Healthier
August 20, 2018 - FDA approves brain stimulation device for OCD
August 20, 2018 - NYU Langone’s Perlmutter Cancer Center expands Blood and Marrow Transplant Program
August 20, 2018 - New drug shows potential to prevent painful side effect of therapy
August 20, 2018 - RDMD raises $3 million in seed funding to accelerate rare disease research, drug development
August 20, 2018 - Illicit drug use is higher during celebratory events, may be worse than previously thought
August 20, 2018 - Exploring the relationship between fever and cancer incidence
August 20, 2018 - Study reveals how socioeconomic status affects racial, ethnic disparities in childhood cancer survival
August 20, 2018 - Brain tumors trap immune cells needed to fight cancer in the bone marrow, finds research
August 20, 2018 - Three factors that contribute to physician burnout
August 20, 2018 - Babies dependent on opioids need touch, not tech
August 20, 2018 - Understanding How Antibodies Shape the Gut Microbiome
August 20, 2018 - Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
August 20, 2018 - Kidney transplant chains more effective in saving lives
August 20, 2018 - Study unravels cellular and molecular mechanisms behind dermal condensate formation
August 20, 2018 - New integrated gene logic-chips could have great value in medical care
August 20, 2018 - FDA Advisory Committee Recommends Approval of Paratek’s Omadacycline
August 20, 2018 - Total, open repairs decline for abdominal aortic aneurysms
August 20, 2018 - Novel system can pinpoint ingestible implants inside the body using wireless signals
August 20, 2018 - Infection rates of high risk oral HPV in England found to be lower than expected
August 20, 2018 - Making robots as valuable and trustworthy assistants for medical therapies
August 20, 2018 - Patients with low-risk blood clots can be better treated at home than at hospital
August 20, 2018 - Passive smoking exposure among kids greatly increases COPD risk late in life
Cocaine relapse is reversed with BDNF microinjections in the brain

Cocaine relapse is reversed with BDNF microinjections in the brain

image_pdfDownload PDFimage_print
Ana Clara Bobadilla, Ph.D. is first author on the Addiction Biology article. Credit: Sarah PackMedical University of South Carolina

Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.

“We discovered that a very common protein in the brain has an additional significant role in addiction relapse,” says lead author Ana-Clara Bobadilla, Ph.D., a postdoctoral scholar in the laboratory of Peter Kalivas, Ph.D., at MUSC.

The nucleus accumbens is a tiny cluster of nerve cells deep in the brain. Although small, this region plays a critical role in reward-seeking behaviors. The nucleus accumbens combines signals from other parts of the brain to drive reward-motivated behaviors. The MUSC research group is the first to reveal that BDNF has both a time- and location-dependent beneficial role when administered before a cue-induced relapse event.

In the preclinical model of cocaine addiction, rats are allowed to self-administer cocaine while hearing an auditory cue. The rats learn to associate the cue with the reward of cocaine and continue to self-administer when hearing the cue. In the extinction phase, the rats are not allowed access to cocaine or the cue associated with the drug. In the last phase, called reinstatement, the rats seek out cocaine upon hearing the cue previously associated with cocaine administration. The drug-seeking behavior that the rats display is similar to how drug cues induce craving in humans and thus are more likely to relapse. Examples of such cues are visiting a neighborhood in which drugs were previously bought or seeing a friend with whom they took drugs.

Addiction researchers are studying the function of proteins already present in the brain in an effort to find ways to overcome relapse in strong addictions. One common protein, BDNF, is a small protein with a big job. It plays essential roles in neuron development and memory in multiple brain regions. While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.

“An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”

The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse. “The most exciting realization is that this protein has a very fine-tuned effect and can be timing dependent” says Bobadilla. This means that by changing the location of BDNF administration in the brain, as well as the timing of the treatment, BDNF can have differing impacts on cocaine relapse.

This discovery opens the doors for further investigation with BDNF and the nucleus accumbens in particular, as it is currently not known how BDNF suppresses cocaine addiction relapse. This finding also begs the question as to whether BDNF application in the nucleus accumbens, or other brain regions, can reduce other addictions. The MUSC research team also found that the BDNF—nucleus accumbens connection is included in the reward circuit but remains specific to drug rewards, since BDNF did not stop food-seeking behaviors, which also activate the reward circuitry. This demonstrates that BDNF’s inhibitory role on seeking is specific to drugs of abuse.

These findings fill in one more piece of the puzzle of addiction by highlighting that a common protein in the brain can have very different roles depending upon the location and reward circuit activated. The Kalivas laboratory will continue this investigation by looking at the role of BDNF on the different types of neurons included in the nucleus accumbens in the context of BDNF application during addiction relapse.

“What we are doing with these studies is mapping the brain. There are plenty of uncharted territories in our understanding of neurobiology and with this work we provided results to fill in one of those unknown questions.” says Bobadilla. She envisions that one day we will have a complete map of the brain, and when we do, preventing addiction relapse may be possible.


Explore further:
Morphine and cocaine affect reward sensation differently

More information:
Ana-Clara Bobadilla et al, Accumbens brain-derived neurotrophic factor (BDNF) transmission inhibits cocaine seeking, Addiction Biology (2018). DOI: 10.1111/adb.12638

Journal reference:
Addiction Biology

Provided by:
Medical University of South Carolina

Tagged with:

About author

Related Articles