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Gallo Center scientists identify key brain circuits that control compulsive drinking in rats
Date:7/22/2013

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The drinking rats showed a notable increase in the NMDA receptor (NMDAR), which lead author Taban Seif, PhD, a Gallo Center researcher, called a molecule that excites the brain. When the rats were injected with an NMDAR blocker, their consumption of quinine-laced alcohol dropped significantly, while regular alcohol use was unaffected. In other words, only the compulsive drinking was affected, said Seif.

The team then focused its research on connections from two specific regions of the rats prefrontal cortex where they had discovered the presence of unusual types of NMDARs: the medial prefrontal cortex, which mediates conflict during decision-making, and the insula, which is critical for self-awareness and feelings. In a non-addict, these brain areas tell you when something is potentially harmful and bad, and to run away as fast as possible, said Hopf. But if youre a compulsive drinker, it seems instead that they give you a comforting pat on the back, in effect telling you its OK to have another drink, nothing to worry about.

Using a technique called optogenetics, the scientists inserted halorhodopsin, a light-sensitive protein, into these areas. They then used fiber-optic cables implanted in the rats brains to send pulses of laser light that activated the halorhodopsin, which in turn inhibited the regions connections to the nucleus accumbens. The researchers found that rats inhibited in this way drank significantly less quinine-laced alcohol, while their intake of regular alcohol solution remained unaffected.

The fact that we reduced the rats compulsive drinking using two different methods an NMDAR blocker and direct inhibition of connections tells us that we have probably identified the right areas, said Hopf.

The next logical step for the research team, said Hopf, would be to work with clinical researchers on an NMDAR blocker trial in human subjects.

What is interesting is t
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Contact: Jeffrey Norris
jeff.norris@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert

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