Navigation Links
Scripps Research scientists find key mechanism in transition to alcohol dependence
Date:5/31/2011

A team of Scripps Research Institute scientists has found a key biological mechanism underpinning the transition to alcohol dependence. This finding opens the door to the development of drugs to manage excessive alcohol consumption.

"Our focus in this study, like much of our lab's research, was to examine the role of the brain's stress system in compulsive alcohol drinking driven by the aversive aspects of alcohol withdrawal," said Scripps Research Associate Professor Marisa Roberto, Ph.D., senior author of the study.

"A major goal for this study," added Research Associate Nicholas Gilpin, Ph.D., the paper's first author, "was to determine the neural circuitry that mediates the transition to alcohol dependence."

In the new research, published in the June 1, 2011 issue of the journal Biological Psychiatry, the Scripps Research scientists demonstrated the key role of a receptor a structure that binds substances, triggering certain biological effectsfor neuropeptide Y in a part of the brain known as the central amygdala. The amygdala, a group of nuclei deep within the medial temporal lobes, performs an important role in the processing and memory of emotional reactions.

"We've known for quite some time that neuropeptide Y is an endogenous [naturally occurring] anti-stress agent," says Markus Heilig, clinical director of the National Institute of Alcohol Abuse and Alcoholism (NIAAA). "We've also known that development of alcohol dependence gives rise to increased sensitivity to stress. This paper elegantly and logically brings these two lines of research together. It supports the idea that strengthening neuropeptide Y transmission in the amygdala would be an attractive treatment for alcoholism. The challenge remains to develop clinically useful medications based on this principle."

Discovering the Circuitry

Building on Gilpin's previous work on neuropeptide Y, in the new project, Gilpin, Roberto, and colleagues observed the effects of the administration neuropeptide Y in the central amygdala on alcohol drinking in rats. Alcohol-dependent rats were allowed to press levers for ethanol and water during daily withdrawal from chronic alcohol exposure.

"Normally, the transition to alcohol dependence is accompanied by gradually escalating levels of alcohol consumption during daily withdrawals," Gilpin explained. "The aim of this protocol was to examine whether neuropeptide Y infusions during daily withdrawals would block this escalation of alcohol drinking."

The scientists report a suppression of alcohol consumption with chronic neuropeptide Y infusions and detailed some of the neurocircuitry involved. Ethanol normally produces robust increases in inhibitory GABAergic transmissionGABA is another neurotransmitterin the central amygdala, but this effect is blocked and reversed by neuropeptide Y.

Gilpin notes the scientists were surprised at one aspect of the findingsthe role of a subset of neuropeptide Y receptors known as Y2 receptors. "Previous behavioral evidence suggested that antagonism of Y2 receptors in whole brain suppresses alcohol drinking, similar to the effects of neuropeptide Y," he said. "However, our data suggest that Y2 receptor blockade in central amygdala might actually increase alcohol drinking, presumably by affecting pre-synaptic release of GABA. These data also suggest that antagonism of post-synaptic Y1 receptors in central amygdala provides a viable pharmacotherapeutic strategy, a hypothesis supported by previous work from other labs."

Two additional aspects of the findings are worth noting, Roberto says. First, repeated neuropeptide Y administration not only blocked the development of excessive alcohol consumption in dependent rats, but also tempered the moderate increase in alcohol consumption following periods of abstinence in non-dependent rats. Second, neuropeptide Y exhibited long-term efficacy in suppressing alcohol self-administration, highlighting the potential of neuropeptide Y treatments for a clinical setting.


'/>"/>

Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Related biology news :

1. Scripps research team solves structure of beneficial virus
2. Scripps research team sheds light on immune system suppression
3. Scripps Florida scientists awarded $1.5M to fight major water and food parasites
4. Scripps research scientists identify compounds for stem-cell production from adult cells
5. Scripps research scientists identify blood component that turns bacteria virulent
6. Scripps research team defines new painkilling chemical pathway
7. Dolphin population stunted by fishing activities, Scripps/NOAA study finds
8. Scripps Research scientists shed light on how DNA is unwound so that its code can be read
9. Scripps scientists develop first examples of RNA that replicates itself indefinitely
10. Scripps scientists create first crystal structure of an intermediate particle in virus assembly
11. Historical photographs expose decline in Floridas reef fish, new Scripps study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/3/2017)... , April 3, 2017  Data captured ... engineering platform, detected a statistically significant association ... prior to treatment and objective response of ... potential to predict whether cancer patients will ... treatment, as well as to improve both pre-infusion ...
(Date:3/29/2017)... , March 29, 2017  higi, the health ... in North America , today announced ... and the acquisition of EveryMove. The new investment and ... set of tools to transform population health activities through ... lifestyle data. higi collects and secures data ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Global ... to 2025" report to their offering. ... The Global Biometric Vehicle Access System Market ... the next decade to reach approximately $1,580 million by 2025. ... for all the given segments on global as well as regional ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ComplianceOnline’s Medical Device Summit is back for its ... 2018 in San Francisco, CA. The Summit brings together current and former FDA office ... directors and government officials from around the world to address key issues in device ...
(Date:10/11/2017)... ... 11, 2017 , ... A new study published in Fertility ... fresh in vitro fertilization (IVF) transfer cycles. The multi-center matched cohort ... After comparing the results from the fresh and frozen transfer cohorts, the authors ...
(Date:10/10/2017)... ... 10, 2017 , ... Dr. Bob Harman, founder and CEO of VetStem ... The event entitled “Stem Cells and Their Regenerative Powers,” was held ... Harman, DVM, MPVM was joined by two human doctors: Peter B. Hanson, M.D., Chief ...
(Date:10/9/2017)... , Oct. 9, 2017  BioTech Holdings ... mechanism by which its ProCell stem cell therapy ... limb ischemia.  The Company, demonstrated that treatment with ... of limbs saved as compared to standard bone ... molecule HGF resulted in reduction of therapeutic effect.  ...
Breaking Biology Technology: