Mouse studies offer new insights about cocaine’s effect on the brain

Addiction resistant? When scientists manipulated mice to remove a specific protein from their brain’s reward region, the animals showed a pronounced decrease in their preference for cocaine.

Now the laboratory of Rockefeller University Professor and Nobel Laureate Paul Greengard has shown for the first time in mice how a protein called WAVE1 regulates the brain’s response to cocaine. Their discovery, which was published recently in the journal Proceedings of the National Academy of Sciences, offers fundamental insights into the brain’s inner workings—and could lead to better interventions for treating addiction to cocaine and other drugs.

Cocaine and the brain

Researchers have long used cocaine as a model to study how certain messages are transmitted in the brain. And Greengard’s group, which investigates the molecular basis of communication between nerve cells in the brains of mammals, has studied WAVE1, a protein involved in cell signaling, for more than a decade. But their PNAS study reveals something new about the way in which WAVE1 and dopamine interact.

“We knew about the connection between WAVE1 and dopamine many years ago, but until now no one knew the mechanism of how cocaine stimulates WAVE1 and how WAVE1 regulates cocaine’s actions,” says Yong Kim, a Research Assistant Professor in Greengard’s lab and the senior author of the new study.

No WAVE1, no reward

In the new work, the team observed that WAVE1 became active in the brain of mice exposed to cocaine, and that this cocaine effect on WAVE1 could be prevented by blocking dopamine receptors. The research also provides new clues about how WAVE1 influences changes in the brain’s synapses— the junctions between nerves through which impulses pass—in response to cocaine exposure.

Specifically, the investigators looked at changes in an area of the brain called the nucleus accumbens, a key component of the neural reward system that is known to play a critical part in addiction—and in which dopamine is heavily involved. When these synapses form, they allow the signals from dopamine and another neurotransmitter called glutamate to be transmitted.

To investigate the interaction between WAVE1 and dopamine more specifically, the team looked at mice that had WAVE1 selectively removed in nerve cells. These nerve cells also contained one of the subtypes of dopamine receptor (called D1). They found a significant decrease in the preference for cocaine in these mice, compared with those producing normal WAVE1 levels.  This suggested that the dopamine signals were not being transmitted.

However, this effect was not seen when WAVE1 was removed from nerve cells containing a different dopamine receptor subtype (called D2). Those results suggest previously unknown details about how cocaine works.

Addiction intervention

“It’s well known that cocaine increases the signaling of dopamine in the brain,” Kim says. “Understanding more about the mechanism of cocaine action is providing new insight into the neurobiology of addiction. Our eventual goal is to use these findings to find a way to develop a drug to treat addiction.”

However, Kim says there are limitations to the current work, largely because the mice were injected with cocaine by the researchers. Future studies will need a system in which the mice can self-administer the cocaine by pushing a lever and injecting themselves, a model that more closely mimics human addiction behavior.

This work was supported by grants from the Department of Defense (USAMRAA W81XWH-09-1-0392 and W81XWH-09-1-0402), the National Institutes of Health (DA010044, MH090963, R01DA014133 and NS34696), and the JPB Foundation.


Yahoo Studies Bids for Assets as Losses Mount

Yahoo Studies Bids for Assets as Losses Mount

Yahoo offered no definitive word Monday on bids for the key assets of the faded Internet star, as it reported widening losses in the past quarter.

In its quarterly earnings update, Yahoo made no comment on the results of the widely reported bidding efforts for its core Internet operations.

Chief executive Marissa Mayer said in the earnings webcast that “we have no announcement today” on the bidding, but noted that “we are deep into the process of evaluating all the proposals.”

Some media reports said the deadline for bids was Monday and that Yahoo would decide soon on its course of action.

The earnings report, which according to some analysts may be the last for Yahoo under its current structure, showed its loss in the second quarter widened to $440 million from $22 million a year earlier.

Revenue rose slightly to $1.3 billion from $1.24 billion a year earlier, the company said.

The results reflected its “lowest cost structure and headcount in a decade,” Mayer said in a statement.

“We continue to make solid progress against our 2016 plan. Through disciplined expense management and focused execution, we delivered Q2 results that met guidance across the board and in some areas exceeded it.”

Maximizing value
Mayer said that even with a bidding process ongoing, she is hoping to revive growth in key areas and cut costs, saying “it is important to maximize the value of Yahoo in any scenario.”

She said this effort involves “simplifying the business and efficiently aligning our resources.”

But Yahoo’s future is far from certain, amid intense speculation about efforts to sell its main assets.

The company has been pursuing its strategic review amid pressure from shareholders to salvage what is left of a company that was once a leader in the online space but has been overtaken by Google and Facebook.

In April, Yahoo averted a proxy battle for control of the company with a compromise Wednesday that added four new board members, including a hedge fund chief who has been critical of management.

The deal was reached with Starboard Value, which had launched a bid to replace the entire board of the Internet giant.

Yahoo has not commented on any specific bidders for the core business, but much of the speculation centres around Verizon, the telecom giant which recently acquired another faded Internet star, AOL.

Another likely bidder is Quicken Loans founder Dan Gilbert, backed by billionaire Warren Buffett.

In February, Yahoo said it was cutting 15 percent of its workforce and narrowing its focus as it explored alternatives.

Mayer has simultaneously been working to revive growth and made priorities of what she refers to as “Mavens” – mobile, video, native advertising and social media.

But according to the research firm eMarketer, Yahoo will earn just 1.5 percent of net digital ad revenues worldwide this year, down from 2.1 percent in 2015.

The company is not only losing share of the market, but is also raking in fewer ad dollars in absolute terms, according to the research firm.

BGC analyst Colin Gillis said in a research note last week that Yahoo’s core assets would be sold for relatively little.

“We expect any offer in the range of $5-plus billion should be accepted by the Yahoo board to bring the process to a close,” he said.

“Yahoo is over in our eyes.”

Tags: Apps, Internet, Marissa Mayer, Sale, Tumblr, Yahoo

Matt Damon stocks studies Which Helped Him shape His life

Matt Damon

Matt Damon become speaking at the Institute of era in Cambridge
Matt Damon shared his experiences of his auditions with Ben Affleck
don’t agree with the hype it is thrown at you,” said Matt Damon
Actor Matt Damon stated that he has no troubles approximately failing as he feels it has shaped himgreater than his successes, pronounced

The Martian superstar has entreated students graduating from the Massachusetts Institute of generation in Cambridge to not worry about being knocked down a peg or every so often because it failure shapes whoyou’re.

you’re going to fail every so often, and that’s an excellent thing,” stated Mr Damon.

“For all the extremely good successes i’ve been lucky to share in, few things have shaped me greaterthan the auditions that Ben (Affleck) and i used to do as younger actors – wherein we would get on a bus,show up in ny, look ahead to our turn, cry our hearts out for a scene, and then be told, ‘adequate,thanks.’ that means: game over. We used to name it ‘being good enough thanksed’. those experiencesbecame our armour,” said Mr Damon.

The 45yrvintage actor additionally admitted he has had his very ownproportion of terrible ideasover time.

Mr Damon stated: “well, you’re that freaking clever! however don’t trust the hype it is thrown at you. Youdo not have all the answers. and also you should not. and that’s first-class.”

you’re going to have your share of bad ideas. For me, one changed into gambling a person named ‘Edgar Pudwhacker’. I want I ought to let you know i am making that up. however as the fantasticlogician, Benjamin Affleck, once said, ‘choose me with the aid of how appropriate my desirable ideasare, not through how terrible my bad ideas are’,” he said.

Director of Donald Trump’s Campaign Says He Would Legislate Against Liberal Arts Studies

Director of Donald Trump’s Campaign Says He Would Legislate Against Liberal Arts Studies

While many in the education community collectively agree that liberal arts studies have an important place in a well-balanced education, Donald Trump’s campaign revealed recently that the controversial nominee would actively make it harder for students to pursue those kinds of studies. “Sam Clovis, the national co-chair and policy director of Trump’s campaign, outlined for Inside Higher Ed the ideas that the presumptive GOP nominee is preparing to put forth,” said Slate Magazine. Part of that included making it “harder for those wanting to major in the liberal arts at non-elite institutions to obtain loans.” When outlining the policies, Clovis reportedly acknowledged that many of Trump’s education policies will be highly criticized and even fought against. “Clovis said he expects some higher education leaders to react the same way as Trump outlines these ideas in the fall campaign. He said the campaign remains open to ideas as long as they put the emphasis on student success in ways that have more impact than efforts of past administrations,” the article said. Later on in the article, Clovis spoke more bluntly about his and Trump’s thoughts on liberal arts. “If you are going to study 16th century French art, more power to you. I support the arts … But you are not going to get a job,” he said. He went onto say while liberal arts is important for subjects like engineering and business, there are “issues” with strictly focusing in a given liberal arts subject unless a student is go to a prestigious university like Harvard. Clovis had other controversial things to say, as well. When it comes to the subject of free higher education or plans to help students graduate debt-free, Clovis said Trump is an “unequivocally no” on that one. Read the full story. Nicole Gorman, Education World Contributor