Stress steroid mediated withdrawal anxiety in dependent rats reversible by flumazenil
2013-10-07
(Press-News.org) Brooklyn, NY (October 7, 2013) – SUNY Downstate Medical Center announced today that Sheryl Smith, PhD, professor of physiology and pharmacology, has published new findings demonstrating a reproducible pathology that may help shed light on anxiety and mood volatility in methamphetamine dependence. In her animal study, Dr. Smith demonstrates that neuroactive stress steroids can trigger identifiable changes to the brains of methamphetamine dependent rats in withdrawal. Interestingly, Dr. Smith notes, these changes appear to be reversible by an existing pharmacological agent – flumazenil. The paper, titled, "A Stress Steroid Triggers Anxiety via Increased Expression of a4bd GABAA Receptors in Methamphetamine Dependence," was recently published online in Neuroscience.
"Methamphetamine is an addictive stimulant drug. Dependence on this drug is difficult to treat because of the severity of the symptoms of methamphetamine withdrawal," said Dr. Smith. "In addition to drug craving and lethargy, withdrawal from methamphetamine is associated with stress-triggered anxiety that may compromise therapeutic intervention. In our recent publication, we show that the system that provides inhibitory control in the brain is dysregulated during methamphetamine dependence in laboratory rodents."
The novel inhibitory receptor that is increased by exposure to methamphetamine is also the target for a stress steroid that produces anxiety during withdrawal from methamphetamine. This receptor is also a novel target for flumazenil, a drug commonly used to treat tranquilizer overdose. Flumazenil reduced expression of the inhibitory receptor and also prevented the anxiety triggered by the stress steroid during methamphetamine withdrawal. These findings suggest a novel mechanism for stress-triggered anxiety in methamphetamine dependence where flumazenil may have important therapeutic value.
One component of the stress response is the release of the steroid allopregnanolone or THP. This steroid modulates GABAA receptors, with α4βδ GABARs the most sensitive target. These receptors are extrasynaptic and generate a tonic current that is neuroprotective. They also exhibit a high degree of plasticity in response to increases in neuronal excitability, which would accompany METH exposure. In some cases, flumazenil was administered during the 24 hour withdrawal period. Although this drug is a benzodiazepine antagonist, it also binds to α4βδ GABARs and has been shown to regulate α4 expression.
The study results show that chronic METH treatment and its withdrawal significantly increased expression of α4 and δ GABAR subunits by 2 to 3-fold. This effect was prevented, however, by flumazenil administration during the withdrawal period.
Dr. Smith continued, "Our results suggest that increased α4βδ GABARs mediate the anxiety response to stress steroids after METH withdrawal, an effect prevented by flumazenil. Because stress-triggered anxiety can result in drug relapse, flumazenil may have important therapeutic benefit in METH dependence."
###
The work in this study was supported by grants from the U.S. National Institutes of Health: DA09618, AA12958 and MH100561, and was also supported by a contract from Hythiam, Inc.
SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient's bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, Colleges of Nursing and Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and an Advanced Biotechnology Park and Biotechnology Incubator.
SUNY Downstate ranks ninth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school.
ELSE PRESS RELEASES FROM THIS DATE:
Carnegie Mellon motion tracking technology is extremely precise, inexpensive with minimal lag
2013-10-07
PITTSBURGH—Researchers at Carnegie Mellon University and Disney Research Pittsburgh have devised a motion tracking technology that could eliminate much of the annoying lag that occurs in existing video game systems that use motion tracking, while also being extremely precise and highly affordable.
Called Lumitrack, the technology has two components — projectors and sensors. A structured pattern, which looks something like a very large barcode, is projected over the area to be tracked. Sensor units, either near the projector or on the person or object being tracked, can ...
Study identifies essential molecule in formation of differentiated blood cells
2013-10-07
CINCINNATI – New research in the Journal of Experimental Medicine identifies a protein that controls the formation of different types of mature blood cells – a finding that could be important to developing new treatments for blood diseases and helping realize the potential of regenerative medicine.
Researchers from Cincinnati Children's Hospital Medical Center report their results in a study published online by the journal Oct. 7. The authors focus on a protein called RhoA, a GTPase that serves as a molecular switch in the cytoplasm of cells to control cell function. ...
Vaccination campaign doubles HBV mutations
2013-10-07
WASHINGTON, DC – October 7, 2013 – A universal infant vaccination campaign in China has led the Hepatitis B virus (HBV) to more than double its rate of "breakout" mutations. These mutations may enable the virus to elude the vaccine, necessitating new vaccination strategies. Researchers at the Chinese Centers for Disease Control and Prevention and University of North Carolina, Chapel Hill, report their findings in an article published ahead of print in the Journal of Virology.
Until a universal vaccination program for infants was implemented in 1992, nearly ten percent ...
'White graphene' halts rust in high temps
2013-10-07
HOUSTON – (Oct. 7, 2013) – Atomically thin sheets of hexagonal boron nitride (h-BN) have the handy benefit of protecting what's underneath from oxidizing even at very high temperatures, Rice University researchers have discovered.
One or several layers of the material sometimes called "white graphene" keep materials from oxidizing – or rusting -- up to 1,100 degrees Celsius (2,012 degrees Fahrenheit), and can be made large enough for industrial applications, they said.
The Rice study led by materials scientists Pulickel Ajayan and Jun Lou appears today in the online ...
What makes triathletes so tough?
2013-10-07
Triathletes participate in a grueling endurance sport, swimming, bicycling, and running long distances without rest. In training and competitions, they regularly push their bodies beyond the limits most of us can endure. But while there is no doubt that triathletes are tough, very little is known about what gives them their exceptional abilities.
Now researchers at Tel Aviv University have discovered a possible explanation. Prof. Ruth Defrin and her doctoral student Nirit Geva of the Department of Physical Therapy at TAU's Sackler Faculty of Medicine have found that triathletes ...
For liberals and conservatives, 'belief superiority' is bipartisan
2013-10-07
DURHAM, N.C. -- As the budget crisis drags on, at least conservatives and liberals have something in common: both believe their views on certain issues are not only correct but all other views are inferior.
A study from Duke University examined whether one end of the American political spectrum believes more strongly than the other in the superiority of its principles and positions. It found both sides have elements of "belief superiority," depending on the issue.
When asked about nine hot-button issues, conservatives feel most superior about their views on voter identification ...
Boston University researchers test effectiveness of treatments for alcoholism and anxiety
2013-10-07
Domenic Ciraulo, MD, chair of psychiatry at Boston University School of Medicine (BUSM) and David H. Barlow, PhD, professor of psychology at Boston University (BU), have collaborated to study the effect of behavioral and medication treatments on patients with alcoholism and anxiety.
The findings, published in the journal Behaviour Research and Therapy, suggest that Transdiagnostic cognitive behavioral therapy (CBT) was more effective in reducing heavy drinking in anxious alcoholics than progressive muscle relaxation therapy (PMR). They also found that the addition of ...
How do stress hormones during pregnancy predict adult nicotine addiction?
2013-10-07
(PROVIDENCE, R.I.) -- Adult women whose mothers had increased levels of stress hormones while they were pregnant are at greater risk of becoming addicted to nicotine, according to a new study led by a Miriam Hospital researcher.
The 40-year longitudinal study provides the first evidence that prenatal exposure to the class of stress hormones known as glucocorticoids predicts nicotine dependence later in life – but only for daughters. It also confirms previous research that babies born to moms who smoked when pregnant have an increased risk of nicotine addiction in adulthood. ...
Numerically identifying pollen grains improves on conventional ID method
2013-10-07
CHAMPAIGN, Ill. — Researchers have developed a new quantitative – rather than qualitative – method of identifying pollen grains that is certainly nothing to sneeze at.
The research appears in the journal Proceedings of the Royal Society B: Biological Sciences.
Since the invention of the earliest light microscopes, the classification and identification of pollen and spores has been a highly subjective venture for those who use these tiny particles to study vegetation in their field, palynology.
However, according to the lead author of the study, Luke Mander, a former ...
Scientists unlock secret of cattle ticks' resistance to pesticide
2013-10-07
Scientists have discovered how a tick which transmits devastating diseases to cattle has developed resistance to one of the main pesticides used to kill it.
Approximately 80% of cattle around the world, mostly in the tropics and sub-tropics, are exposed to the cattle tick – Rhipicephalis microplus – which can cause anaemia, reduced rate of growth and death, resulting in a major economic impact on farmers.
Prevention of disease is through frequent treatment of cattle with acarides –pesticides for ticks and mites – mainly amitraz, ivermectins and pyrethroids, but ticks ...