Findings may help explain why drugs for addiction, depression are not always effective
New research may help explain why drug treatments for addiction and depression don't work for some patients.
A mouse wears a wireless LED device that can activate cells in the brain to produce either reward or aversion responses.
Credit: Bruchas laboratory, Washington University
The conditions are linked to reward and aversion responses in the brain. Working in mice, researchers at Washington University School of Medicine in St. Louis have discovered brain pathways linked to reward and aversion behaviors are in such close proximity that they unintentionally could be activated at the same time.
The findings suggest that drug treatments for addiction and depression simultaneously may stimulate reward and aversion responses, resulting in a net effect of zero in some patients.
The research is published online Sept. 2 in the journal Neuron.
"We studied the neurons that cause activation of kappa opioid receptors, which are involved in every kind of addiction -- alcohol, nicotine, cocaine, heroin, methamphetamine," said principal investigator Michael R. Bruchas, PhD, associate professor of anesthesiology and neurobiology. "We produced opposite reward and aversion behaviors by activating neuronal populations located very near one another. This might help explain why drug treatments for addiction don't always work -- they could be working in these two regions at the same time and canceling out any effects."
Addiction can result when a drug temporarily produces a reward response in the brain that, once it wears off, prompts an aversion response that creates an urge for more drugs.
The researchers studied mice genetically engineered so that some of their brain cells could be activated with light. Using tiny, implantable LED devices to shine a light on the neurons, they stimulated cells in a region of the brain called the nucleus accumbens, producing a reward response. Cells in that part of the bran are dotted with kappa opioid receptors, which are involved in addiction and depression.
The mice returned over and over again to the same part of a maze when the researchers stimulated the brain cells to produce a reward response. But activating cells a millimeter away resulted in robust aversion behavior, causing the mice to avoid these areas.
"We were surprised to see that activation of the same types of receptors on the same types of cells in the same region of the brain could cause different responses," said first author Ream Al-Hasani, PhD, an instructor in anesthesiology. "By understanding how these receptors work, we may be able to more specifically target drug therapies to treat conditions linked to reward and aversion responses, such as addiction or depression."
Funding for this research comes from the National Institute on Drug Abuse, the National Institute on Neurological Disorders and Stroke and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), grant numbers P30 NS057105,
R01 DA033396, R01 DA037152 K99/R00 DA038725, TR01 NS081707 R01 DK075623, R37 DK053477, R01 DK089044, R01 DK071051, R01 DK096010, P30DK046200 and P30 DK057521.
Al-Hasani R, McCall JG, Shin G, Gomez AM, Schmitz GP, Bernardi JM, Pyo CO, Park SI Marcinkiewcz CM, Crowley NA, Krashes MJ, Lowell BB, Kash TL, Rogers JA, Bruchas MR. Distinct subpopulations of nucleus accumbens dynorphin neurons drive aversion and reward. Neuron, published online Sept. 2, 2015.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Jim Dryden | EurekAlert!
Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku
Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy