Chronic morphine exposure has the opposite effect on the brain compared to cocaine in mice, providing new insight into the basis of opiate addiction, according to Mount Sinai School of Medicine researchers.
They found that a protein called brain-derived neurotrophic factor (BDNF), which is increased in cocaine addiction, is inhibited in opioid addiction. The research is published in the October 5 issue of Science.
"Our study shows that BDNF responds completely differently with opioid administration compared to cocaine," said Ja Wook Koo, PhD, Postdoctoral Fellow in the Department of Neuroscience at Mount Sinai School of Medicine. "Morphine creates reward by inhibiting BDNF, whereas cocaine acts by enhancing BDNF activity."
BDNF is key to several functions in the brain and peripheral nervous system, notably for making new nerve cells and helping the survival of existing ones. It is also known to activate reward centers in the brain. Cocaine causes an increase in the presence of BDNF in a reward center of the brain called the nucleus accumbens, which results in activation of the reward center.
In the current study, the research team found that morphine suppresses BDNF in a different reward center of the brain known as the ventral tegmental area (VTA), in order to achieve reward and chronic addiction. The morphine caused a depletion of BDNF in the VTA of mice, which activated the reward centers. However, when BDNF was administered to the VTA of mice, it inhibited that reward. When BDNF was administered to the nucleus accumbens, there was no reward.
When researchers analyzed morphine-induced changes in gene expression in the nucleus accumbens, the area of the brain in which morphine caused no reward or response they found that two genes, sox11 and gadd45g, mediated the brain's response to morphine, preventing any reward and addiction.
"This study provides important insight into the molecular basis for morphine addiction, and is the first to show that BDNF is a negative modulator in brain, especially in opioid addiction, unlike stimulant addiction," said Dr. Koo. "While further research is needed, the genes we identified may be useful targets in preventing addiction." Continuing to study the counteractive response of BDNF in morphine as compared to cocaine may also help researchers determine how poly-drug use may impact the brain.
Dr. Koo is part of the Eric Nestler, MD,PhD laboratory at Mount Sinai School of Medicine. Dr. Nestler is the Nash Family Professor and Chair of Neuroscience and Director of the Friedman Brain Institute at Mount Sinai. Students in the Mount Sinai Graduate School of Biological Sciences also participated in the research, including Haosheng Sun and Diane Damez-Werno.
This study was supported by grants from the National Institute on Drug Abuse and a Rubicon Grant from the Dutch Scientific Organization.About The Mount Sinai Medical Center
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.Find Mount Sinai on:
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences