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Scripps Research scientists find seizure drug reverses cellular effects
Date:5/28/2008

nalogue of the inhibitory synaptic transmitter gamma aminobutyric acid (GABA)on neural signaling in the brain.

In the new study, the scientists first tested the effects of gabapentin on the behavior of alcohol-dependent and non-dependent rats. The researchers found that alcohol-dependent rats that received gabapentin drank significantly less alcohol and demonstrated fewer anxiety-like behaviors in the face of alcohol abstinence than those who did not receive the drug. The behavior of non-dependent rats receiving gabapentin remained unaffected. These results were observed both when the rats received gabapentin systemically and when the medication was infused directly into the central amygdala region of the brain.

At the cellular level, dependence on alcohol has been associated with increased strength of inhibitory synapses (junctions between two nerve cells) in the central amygdala. In the new study, the scientists found gabapentin, like alcohol, increased the strength of these central amygdala inhibitory synapse cells from non-dependent rats, but decreased their strength in cells from alcohol-dependent rats.

Interestingly, these effects of gabapentin disappeared in the presence of a specific inhibitor of so-called GABAB receptors, indicating that gabapentins cellular mechanisms likely involve changes in release of the transmitter GABA at the inhibitory synapses. The scientists also found that the sensitivity of GABAB receptors decreased with alcohol dependence, suggesting a biological mechanism for the development of alcohol dependence in general and for gabapentins contrasting effects before and after long-term alcohol exposure in particular.

The scientists plan to further explore the mechanism of action of gabapentin in the brain. In addition, clinical trials on the effectiveness of gabapentin as a treatment for alcohol dependence are currently under way at The Scripps Research Institute.


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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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