Humans, Apes, Addicts, and Microbes: Their Common Thread

The common thread that links life on Earth is the thin thread of DNA that coils, circles, and works its way through the generations, through the species, changing the face of the planet as it evolves.

Economist
Our brains are formed by our genes, working through the environment. Some genes control an entire platoon of other genes. The genes that determine how our brains grow and function are still evolving. If these "commander" genes evolve, remarkable changes can occur over a fairly short time span. The human species appears to be changing on a more rapid time scale than most scientists are willing to accept.

...human beings have suites of genes that probably cause their brains to be “plastic” and thus receptive to change far longer (to the age of about five) than is true for chimps or monkeys (whose brains are plastic for less than a year after birth). Moreover, Dr Khaitovich was able to work out how the expression of these modules of genes was co-ordinated, by looking at the switches, known as transcription factors, that turn them on and off.

Indeed, by comparing modern genomes with their discoveries about Neanderthals Dr Paabo’s group has found that the regulatory process for one of the modules came into existence after the modern human and Neanderthal lines separated from one another, about 300,000 years ago. _Economist

Of course, it does no good to have brains that are more plastic, if the caregivers of young children do not take advantage of that period of plasticity to give the children skills, competencies, wisdom, and knowledge that will serve them well throughout their lives.

Some people may be born at a tremendous disadvantage, genetically speaking. Addictive and criminal behaviour appear to be at least partially heritable. Societies deal with these problems in different ways. There is always room for improvement -- beginning with the acknowledgement of the genetic component.

Humans have turned a corner in understanding their own genetics. They can now re-program the genes of living humans, and are on the verge of re-programming the genes of embryos and zygotes. Artificial evolution, in other words.

Humans are also making progress toward understanding the complex genetics of their environments -- the microbial world in which they are immersed. We live in microbial soup, which is quite difficult to sort out with the old genetic tools that required culturing organisms before their genomes could be sequenced.

Now, scientists can extract individual genomes out of the common slurry, and sequence these mystery guests.

To extract individual genomes, Armbrust’s PhD student Vaughn Iverson exploited skills that had he gained as a computer scientist designing video compression technology at Intel in Portland, Oregon. He developed a computational method to break the stitched metagenome into chunks that could be separated into different types of organisms. He was then able to assemble the complete genome of Euryarchaeota, even though it was rare within the sample. He plans to release the software over the next six months.

It’s a different tack from that taken by early marine metagenomics efforts, which began in earnest with Craig Venter’s Global Ocean Sampling effort in 20032. “Our survey offered a broad-stroke picture of microbial diversity and the dominant players in the world’s oceans,” says Kenneth Nealson, director of the microbial and environmental genomics group at the J. Craig Venter Institute in San Diego, California. “This clever approach demonstrates that they can pull out the sequence of uncultured organisms — information we need to get a clue as to how microbes share limiting resources in the ocean.” _Nature

We finally understand that it is necessary to understand the full complement and range of genomics, genetics, and epigenetics in which we live -- and how we interact with this milieu in order to work out our lives.

Genetics and evolution have been underrated and ignored by most human intellectuals. But no one -- including these neglectful intellectuals -- is ignored by the genetic universe we inhabit. Not one living thing.

Cross-posted from Al Fin, the Next Level

Clear Genetic Links to Poor Impulse Control, Drug Dependency

University of Michigan medical researchers have identified genetic links to aberrant brain function leading to alcohol and drug dependencies.

The results, published online April 12 in Molecular Psychiatry, suggest that variations in the GABRA2 gene contribute to the risk of alcoholism by influencing impulsive behaviors, at least in part through a portion of the cerebral cortex known as the insula, says study senior author Margit Burmeister, Ph.D., research professor at U-M's Molecular and Behavioral Neuroscience Institute.

...Individuals under distress who also have the risky genetic variant tend to act impulsively, a behavior that may lead to the development of alcohol problems, says lead author Sandra Villafuerte, Ph.D., a research investigator at U-M's Molecular and Behavioral Neuroscience Institute and Department of Psychiatry.

"Developing deeper understandings of the various genetic and environmental factors involved in risky behaviors may guide prevention and treatment efforts in the future," Villafuerte says.

The study included 449 people, who came from 173 families – 129 of whom had at least one member diagnosed with alcohol dependence or abuse. Those with certain variations in the GABRA2 gene were more likely to have alcohol dependence symptoms and higher measures of impulsiveness in response to distress, the study found. Stronger associations were found in women than in men.

...Researchers also used functional magnetic resonance imaging (fMRI) to observe changes of blood flow in the brains of 44 young adults from these families as they performed a task in which they anticipated winning or losing money.

"The neuroimaging allowed us to see for the first time how these genetic variants create differences in how the brain responds in certain situations," says Mary M. Heitzeg, Ph.D., a research assistant professor in U-M's Department of Psychiatry and U-M's Addiction Research Center.

They found that individuals with one form of the GABRA2 gene associated with alcoholism showed significantly higher activation in the insula when anticipating rewards and losses than those with other combinations. This higher activation was also related to a greater level of impulsiveness in response to distress.

..."We believe these results suggest GABRA2 exerts an influence on an underlying neural system that impacts early risk factors and, later, alcohol dependency," says Burmeister, also a professor of psychiatry and human genetics at the U-M Medical School. "In the future, we hope to further examine the effects of family environment and other behavioral and environmental factors." _PO

Genetic influences on behaviours are too numerous to count, yet are extremely difficult to pin down with specificity. That is because multiple causes at several different levels are influencing the events which we observe. It will take many years to sort the many levels of causation -- many of them circular (incorporating feedbacks) in nature.

Persons who are indoctrinated into the religion of political correctness tend to eschew all discussion of genetic influences on behaviour. Funding for research can be difficult to obtain if highly indoctrinated "ethicists" feel that the valid findings of the research may be misconstrued in a way as to contradict politically correct dogma.

But such a PC approach only dooms persons who suffer from genetic disadvantages of behaviour to lifetimes of suffering. Much better to learn everything we can about these phenomena, so as to be able to compensate for these genetically based behavioural and cognitive disadvantages on as many levels as possible.

One approach to compensating for genetic defects in brain functioning is to run a low level dc current through the skull into the brain.

Feeding Stress: Sweet-Cycling the Amygdala

The central amygdala is involved in fear, stress, and anxiety responses. Researchers at Scripps have discovered that the central amygdala's stress response is elevated 5X when a dieter accustomed to sweet foods is switched to normal chow.

"We found that rats cycled in this way between palatable food and less tasty, but otherwise acceptable, food, begin to binge on the sweet food, stop eating their regular food, and show withdrawal-like behaviors often associated with drug addiction. As in addiction to drugs or ethanol, the brain's stress system is involved in each of these changes."


...the researchers looked at the involvement of the brain's stress system -- which had been shown to contribute to patterns of drug and alcohol binging and withdrawal -- in underpinning these behaviors.


To do this, the team measured levels of stress-related corticotropin-releasing factor (CRF) mRNA and peptide in an area of the brain known as the central amygdala, which is involved in fear, anxiety, and stress responses. Indeed, the researchers found that the diet-cycled group on normal chow displayed five times the control group's levels of CRF. Only when the diet-cycled group was fed sweet food did CRF levels return to normal.


"CRF is a key stress neuropeptide," said Cottone. "In observing the activation of the amygdaloid CRF system during abstinence from sweet foods, we understood the causes of recurrent dieting failures."


...To confirm these results and to see whether blocking CRF could reverse some of the effects of diet cycling, the researchers turned to a compound called R121919 (a small molecule CRF1 receptor antagonist).


When administered to the diet-cycled rats, the compound blunted the bingeing on sweet chow, as well as the lackluster pursuit of regular chow and the anxiety-associated behaviors during this part of the diet cycle. As in similar studies modeling alcoholism, on a molecular level diet-cycled rats showed greater sensitivity to the ability of the CRF1 receptor antagonist to reduce central amygdala synaptic transmission of the neurotransmitter GABA, which plays an important role in regulating neuronal excitability. _SD

Very interesting.   High levels of stress underlie many addictions.  Of course, these are rats, not people.  It looks as if the same sort of CRF receptor blocker can blunt addictive behaviours in humans -- to foods, drugs, and other dysfunctional behaviours. We might soon see 13 step anti-addiction programs opening up.  The 13th step would be the use of CRF receptor bloockers.

Do you think they could put those blockers in ice cream?

ABC: Addiction Behaviour Complex -- Solved?

The term "addiction" is used in many contexts to describe an obsession, compulsion, or excessive psychological dependence, such as: drug addiction (e.g. alcoholism), video game addiction, crime, money, work addiction, compulsive overeating, problem gambling, computer addiction,nicotine addiction, pornography addiction, plastic surgery addiction, etc. _Wikipedia

The addiction behaviour complex (ABC) manifested by addicts does not depend upon the object of addiction. In fact, scientists at the University of Toronto and Brigham Young University have discovered that addiction behaviour needs no "object of addiction" to take place! Addictions of all types turn humans into zombies and destroy the economies of homes and communities. What if mind science and medicine could bypass the specific addiction, and eliminate the underlying ABC itself? First we have to understand the ABC.

The Toronto team noted that a single injection of BDNF made rats behave as though they were dependent on opiates (which they had never received). Though rats instinctively prefer certain smells, lighting and texture, these rats left their comfort zone in search of a fix.

"This work may reveal a mechanism that underlies drug addiction," said lead author Hector Vargas-Perez, a neurobiologist at the University of Toronto.

The BYU team confirmed that the protein is a critical regulator of drug dependency. After the BDNF injection, specific chemicals that normally inhibit neurons in this part of the brain instead excited them, a "switch" known to occur when people become dependent on drugs.

Steffensen, who teaches in BYU's psychology department, says this work suggests that BDNF is crucial for inducing a drug dependent state, one important aspect of drug addiction. _SD

Now that neuroscientists possess the tools to better understand the mechanisms of addiction, the possibility of mitigating or even eliminating ABC -- all destructive addiction behaviours -- seems very real. In fact, the obsessions and compulsions of common addictions have clear parallels in a large number of dysfunctional behaviours. What we are talking about is getting at the core of counter-productive obsessions and compulsions -- removing the bad drivers of addictive behaviours of all types.

The cost of addiction is high, and is paid by all members of society at every age:

People of all ages suffer the harmful consequences of drug abuse and addiction.

* Babies exposed to legal and illegal drugs in the womb may be born premature and underweight. This drug exposure can slow the child's intellectual development and affect behavior later in life.6
* Adolescents who abuse drugs often act out, do poorly academically, and drop out of school. They are at risk of unplanned pregnancies, violence, and infectious diseases.
* Adults who abuse drugs often have problems thinking clearly, remembering, and paying attention. They often develop poor social behaviors as a result of their drug abuse, and their work performance and personal relationships suffer.
* Parents' drug abuse often means chaotic, stress-filled homes and child abuse and neglect. Such conditions harm the well-being and development of children in the home and may set the stage for drug abuse in the next generation. _DrugAbuse.gov

The other side of the coin is that many people benefit from the myriad self-destructive compulsive behaviours that people exhibit. Drug lords, politicians, the prison industry, drug enforcement agencies, the mental health industry, government lotteries, casinos, the entertainment and news medias, and many other common fixtures of daily life and quasi-criminality too numerous to delineate.

Of course if you understand the heart of addiction, you can not only "cure" addictive behaviours, you can also reinforce them and condition them around particular environmental stimuli. In other words, not only can you turn zombies back into normal people -- you will also be able to turn normal people into zombies with great skill. It is the dilemma of knowledge, played out on yet another stage.

Cocaine Drug Runners Forced to Go Semi-Submersible

Radar and aerial drug surveillance has grounded most drug smuggling flights, and forced drugrunners to resort to sea routes. For long distance runs from South America to the Caribbean, (Puerto Rico and Cuba are two stopover islands used) boats with low radar profiles are preferred. Semi-submersibles have become quite popular with drugrunners--capable of carrying several tons of cocaine--but the Colombian Navy may have picked up a few tricks from the US Coastguard on detecting these sneaky boats.

The Colombian Navy took down another cocaine carrying submarine [PHOTO], off the Pacific coast. This sub appeared to be carrying several tons of cocaine, but the crew of four scuttled the craft before the navy could capture it. The water was about 9,000 feet deep where the craft went down. The four crewmen of the submersible were captured, and found to have traces of cocaine on their clothing. The submersible was first spotted by an air force plane, which called in a nearby navy patrol boat. That makes the third cocaine carrying sub to be caught in the last three months. This makes ten such craft the Colombians have captured in the last two years.

Strategy Page by way of The Subreport

The US Coast Guard is also picking up a number of these semi-submerisbles along the drug seaways between S. America and US waters.

Coast Guard officials in Alameda, Calif., said a 50-foot semi-submersible craft was spotted Monday by a U.S. Customs and Border Protection surveillance aircraft about 300 miles southwest of the Mexico-Guatemala border. The vessel was abandoned by its crew and sank a short time later, the Coast Guard said. The cocaine bundles bobbed to the surface as a boarding team from the USS DeWert approached to rescue the crew.

"This case shows the challenges our counter-drug patrol forces face, and the lengths to which the drug smuggling organization will go to get their deadly product to the U.S.," said Rear Adm. Craig Bone, tactical commander of U.S. counter drug operations in the Eastern Pacific. "This low-profile semi-submersible craft was very difficult to detect."

Eaglespeak
While you might think that regular submarines would serve better than semi-submersibles, apparently the semi-'s are cheaper, capable of carrying more cargo, and given the limited submersion time of most conventional subs, the semi-'s are almost as stealthy. Unfortunately for the drug interdiction effort, most of the semi-submersibles appear to be getting through--judging by cocaine prices graphed below.The total cocaine market is estimated to be over US$70 Billion. Apparently Venezuela is willing to lend a helping hand to the cocaine trade. Very neighborly of Hugo, eh?

Even at those bargain basement prices, cocaine is profitable enough to allow drug runners to buy new boats (for those lost to interdiction), and there are profits aplenty for distributors to bribe federal and local law enforcement. If you want to know the approximate profits and mark-ups at each step in the cocaine production, and distribution pathway, check out the YouTube graphics below:

The Diversity Scam--Who is Winning, Who is Losing?

Corporations everywhere have force-marched middle managers into training sessions led by "diversity trainers." Most people already knew that the basic idea beneath diversity emerged about 2,000 years ago under two rubrics: Love thy neighbor as thyself, and Do unto others as they would do unto you. Then suddenly this got rewritten as "appreciating differentness."

Source

Yes, corporations, government agencies, and academic institutions are rushing to diversify. Public spokespersons drone on endlessly about the "need to diversify", the "strength in diversification," and so on. The Diversity Industry is a multi-billion dollar institution that is just one of those "sucking sounds" you hear when you listen to North American economies, along with trial lawyers and several other large economic drains on the system. So--what are we getting for all the big money spent on diversification?

[Harvard Prof] Robert Putnam....wrote Bowling Alone, a bestselling book about declining civic engagement. People across the country are clearly disengaging.

Sociologists have even given it a name: Turtling.

Putnam is back, this time with the results of almost 30,000 interviews nationwide. He's not happy with what he has found.

Ever heard the phrase, "Let us celebrate our diversity?"

Putnam has discovered that diversity severely damages civic life. The more diverse the community, the fewer activities people engage in, including voting. They become reluctant to volunteer with charities or arts groups, or to contribute to them.

The greater the diversity, the more residents distrust local leaders and the media -- plus they have little confidence in their own influence. It's not a healthy trend.

At least in the short run, Putnam says, "Immigration and ethnic diversity challenges social solidarity and inhibits social capital."

Translation: The more different we become, the less likely we are to become involved with our communities.

"The more ethnically diverse the people we live around, the less we trust them," Putnam discovered.

Source

You wouldn't expect all the consultants and trainers who are getting rich from diversity training to take all this lying down. They challenged Putnam's findings.

Colleagues and diversity advocates, disturbed at what was emerging from the study, suggested alternative explanations. Prof. Putnam and his team re-ran the data every which way from Sunday and the result was always the same: Diverse communities may be yeasty and even creative, but trust, altruism and community cooperation fall. He calls it "hunkering down."

Source

So other than vested financial and ideological interests, who could possibly still fall for the "diversity scam?" Unfortunately, North American businesses and other employers are rushing headlong into the heart of the scam, investing many billions every year for a system that will only reduce trust of citizens in their communities and co-workers.

North America is addicted to this diversity scam, as it is addicted to many other dysfunctional and counter-productive ideologies. This widespread dysfunctionality--much of it mandated by government agencies--will simply undermine the foundations of workable community, until the individuals who make up society change and grow. I sense a secession movement of some type, building. I call it the next level.

One Pill to Stop Smoking AND Drinking? How'd They Do That?

Smoking tobacco and drinking alcohol go together like sweating and mowing the lawn. So is it really so surprising that a pill that is approved in the US for smoking cessation, may also work as an aid for alcoholics to stop drinking?

The drug, called varenicline, already is sold to help smokers kick the habit. New but preliminary research suggests it could gain a second use in helping heavy drinkers quit, too.

Much further down the line, the tablets might be considered as a treatment for addictions to everything from gambling to painkillers, researchers said.

....Pfizer Inc. developed the drug specifically as a stop-smoking aid and has sold it in the United States since August under the brand name Chantix. Varenicline works by latching onto the same receptors in the brain that nicotine binds to when inhaled in cigarette smoke, an action that leads to the release of dopamine in the brain's pleasure centers. Taking the drug blocks any inhaled nicotine from reinforcing that effect.

A study published Monday suggests not just nicotine but alcohol also acts on the same locations in the brain. That means a drug like varenicline, which makes smoking less rewarding, could do the same for drinking. Preliminary work, done in rats, suggests that is the case.

"The biggest thrill is that this drug, which has already proved safe for people trying to stop smoking, is now a potential drug to fight alcohol dependence," said Selena Bartlett, a University of California, San Francisco neuroscientist who led the study. Details appear this week in the journal Proceedings of the National Academy of Sciences.

Pfizer provided the drug for the study, but was not otherwise involved in the research.

....Several experts not involved in the study cautioned that there is no such thing as a magic cure-all for addiction and that varenicline and similar drugs may find more immediate use in treating diseases like Alzheimer's and Parkinson's.

Source

This is rather fascinating, when you think about it. Of course we all know there is no cure-all for addiction. Otherwise, the inventor of such a cure-all would now be the world's richest person, and we would all have read about it.

Nevertheless, there are few drugs on the market that affect the brain's nicotinic receptor system directly--other than nicotine itself--and this drug is interesting if for no other reason than that. This drug may actually prove to be more effective for treating Alzheimer's Disease than for treating alcoholism--time will tell.

The exact mechanisms of the reward systems in the brain, and how nicotinic receptors are involved, is still being worked out. But the brain's reward system is very central to human motivations and behaviours. This drug and analogs of this drug should prove very useful in ongoing research to tease out the intricacies of these systems.

Important New Neuro-Research Tool--From the Sea

Experimental research in biology and pharmacology proceeds with the discovery of new research tools. Recently, University of Utah researchers discovered a new tool for research into an important neuroreceptor--the nicotinic Acetylcholine receptor. This receptor plays a critical role in the brain, muscle, and autonomic ganglia. This new tool promises to help find new treatments for neurological and neuromuscular diseases that currently cause large scale misery.

University of Utah researchers isolated an unusual nerve toxin in an ocean-dwelling snail, and say its ability to glom onto the brain's nicotine receptors may be useful for designing new drugs to treat a variety of psychiatric and brain diseases.

"We discovered a new toxin from a venomous cone snail that may enable scientists to more effectively develop medications for a wide range of nervous system disorders including Parkinson's disease, Alzheimer's disease, depression, nicotine addiction and perhaps even schizophrenia," says J. Michael McIntosh.

Discovery of the new cone snail toxin will be published Friday, Aug. 25 in The Journal of Biological Chemistry by a team led by McIntosh, a University of Utah research professor of biology, professor and research director of psychiatry, member of the Center for Peptide Neuropharmacology and member of The Brain Institute.

.... McIntosh says the OmIA toxin will be useful in designing new medicines because it fits like a key into certain lock-like "nicotinic acetylcholine receptors" found on nerve cells in the brain and the rest of the nervous system.

"Those are the same types of receptors you activate if you smoke a cigarette," he says, explaining that nicotine in cigarette smoke "binds" to the receptor to trigger the release of a neurotransmitter, which is a chemical that carries a nerve impulse from one nerve cell to another, allowing nerve cells to communicate.

"Nicotine acts on those receptors in our brain, but they are in our brain for better reasons than to enjoy a cigarette," McIntosh says. Different forms or subtypes of nicotinic receptors control the release of different neurotransmitters. "That's important because if you had compounds to facilitate the release of one neurotransmitter and not another neurotransmitter, that opens up medicinal potential," he says.

"For instance, one receptor modifies the release of dopamine. There are inadequate amounts of dopamine in Parkinson's disease," so a medicine designed to fit into a certain subtype of nicotinic receptor would produce more dopamine and thus protect against the development of tremors and other Parkinson's symptoms. Indeed, other studies have found that smoking seems to forestall Parkinson's disease.

A medicine that could block certain nicotinic receptors could be used to help people stop smoking cigarettes, and the same method might work for alcoholism because nicotinic receptors may be involved in alcohol addiction, McIntosh says.

Other nicotinic receptors trigger the release of neurotransmitters involved in memory, so activating the right receptors might lessen Alzheimer's memory loss.

"One reason people smoke is they feel their thinking may be a little better, with increased attention and focus," McIntosh says, noting that pharmaceutical companies "would like to mimic that positive benefit without all the downsides of cigarette smoke."

Other nicotinic receptors influence "the release of serotonin and norepinephrine, two neurotransmitters strongly implicated in mood disorders" such as depression, so a drug to activate those receptors might treat depression, he adds.

Schizophrenics tend to smoke heavily because something in cigarette smoke "seems to help them filter out irrelevant stimuli. They can focus better," McIntosh says. So a drug aimed at certain nicotinic receptors might treat schizophrenia.

....he snails from which the new toxin was obtained were collected by divers in Olivera's native Philippines. Venomous snails use a dart-like tooth to zap fish, snails and other prey, injecting them with an immobilizing toxin. Venom from the collected snails was extracted at a lab in the Philippines, and then sent to Utah.

Once the screening process identified OmIA as promising, McIntosh and colleagues purified the toxin – one of perhaps 200 components in Conus omaria venom. They determined its chemical structure and then synthesized more of the toxin, since they had only a small amount of the natural version.

Next, the synthetic toxin was tested to see how well it acted as a "key" to fit into the "locks" represented both by binding proteins (from freshwater snails and a sea slug) and by actual nicotinic receptors, which came from rat cells but were grown in frog eggs. That allowed the researcher to grow various subtypes of the nicotinic receptors and see how well the toxin fit them.

Taylor and Han provided pictures of the physical structures of the binding protein "locks" and toxin "key," and then "used computer simulation to dock the two structures together," says McIntosh. "That generates a picture of the binding site – the points of contact between the toxin and the binding protein."

The site is the place a new drug would be designed to fit.

"The whole idea is to make the model of the nicotinic receptor so predictive that you can then really speed up the development of drugs," McIntosh says. "If you have an accurate model of the receptor, you can plug in a model of your drugs and do a lot of 'virtual screening.' Rather than synthesizing a million compounds and having all but one be duds, you can synthesize a few thousand compounds based on the model and come up with a better drug with less time and resources."

Source.

It is nice to find new drugs, and new classes of drugs, from nature. Finding a new research tool is even better, since new research tools can lead to new drugs, new classes of drugs, even new approaches to an entire field of study.

Making the World Safe for Drugs Again

If the brain teaches itself to become addicted to a drug such as cocaine, is it possible the brain could "unlearn" the addiction?


In experiments with rat brain slices, the researchers demonstrated that orexin A does increase activity of neurons in the VTA associated with such plasticity.

And in experiments with whole animals, the researchers found that orexin A was required for "behavioral sensitization" to cocaine. This sensitization shows itself as a long-lasting increase in activity by the animals when they receive the drug and is an indicator that the animals are experiencing an increased craving for the drug.

Importantly, when the researchers "microinjected" directly into the VTA region of animals a drug that blocks orexin receptors, they found they could block the development of behavioral sensitization.

"The findings presented here establish a potential mechanism for the role of orexin signaling in plasticity related to addiction," concluded the researchers. The researchers wrote that this orexin-induced plasticity in the VTA "is likely an important substrate of behaviors relevant to addiction, as we show that activation of [orexin] receptors in the VTA is necessary for the development of cocaine-mediated behavioral sensitization. Thus, orexin receptors may provide novel pharmacotherapeutic targets for motivational disorders such as addiction.


Orexins are appetite stimulating peptide hormones secreted by the hypothalamus. But the orexins probably have more important functions than appetite stimulation:

Central administration of orexin A/hypocretin-1 strongly promotes wakefulness, increases body temperature, locomotion and elicits a strong increase in energy expenditure. Sleep deprivation also increases orexin A/hypocretin-1 transmission. The orexin/hypocretin system may thus be more important in the regulation of energy expenditure than food intake.

The association of orexins with plasticity of addiction-related neurons is yet another puzzle to tease out.

If anyone could casually use short acting drugs for amusement, without the worry of addiction, how would that affect society? What about addictions to sex, video games, and the internet? Stay tuned.