Dormivigilia

A few years ago, I read an article about the unfathomable lack of sleep that is structured into the curriculum of military schools; we’re talking 5-6 hours a night for young adults who still requires between 8.4-10 hrs a night. In this month’s journal SLEEP Swedish researchers have observed thatchronic sleep deprivation in military personnel affects moral judgments, in addition to what we already know: decreased reaction time, poor procedural decision making, increased risk taking, increased reliance on hypnotics (alcohol and sleep meds) and psychostimulants (cocaine, amphetamines). Even more shockingly, this chronic sleep deprivation most affected individuals who typically made sound moral decisions. As expected, chronic sleep deprivation had little affect on those individuals who were already lacking in moral fiber. The quality of one’s moral fiber was based from decision-based questionnaires in response to a presented scenario that modeled Kohlberg’s stages of moral development.

No, they weren’t trivial moral decisions like this.

But rather in response to the following scenario:
A woman was near death from a special kind of cancer. There was one drug that the doctors thought might save her. It was a form of radium that a druggist in the same town had recently discovered. The drug was expensive to make, but the druggist was charging ten times what the drug cost him to produce. He paid $200 for the radium and charged $2,000 for a small dose of the drug. The sick woman’s husband, Heinz, went to everyone he knew to borrow the money, but he could only get together about $ 1,000, which is half of what it cost. He told the druggist that his wife was dying and asked him to sell it cheaper or let him pay later. But the druggist said, “No, I discovered the drug and I’m going to make money from it.” So Heinz got desperate and broke into the man’s store to steal the drug for his wife. Should Heinz have broken into the laboratory to steal the drug for his wife? Why or why not?

One typically argues the ethos of this situation by using one of these stages….
Stage one (obedience): Heinz should not steal the medicine because he would consequently be put in prison, which would mean he is a bad person. Or: Heinz should steal the medicine because it is only worth $200, not how much the druggist wanted for it. Heinz had even offered to pay for it and was not stealing anything else.

Stage two (self-interest): Heinz should steal the medicine because he will be much happier if he saves his wife, even if he will have to serve a prison sentence. Or: Heinz should not steal the medicine because prison is an awful place, and he would probably languish over a jail cell more than his wife’s death.

Stage three (conformity): Heinz should steal the medicine because his wife expects it; he wants to be a good husband. Or: Heinz should not steal the drug because stealing is bad and he is not a criminal; he tried to do everything he could without breaking the law, you cannot blame him.

Stage four (law-and-order): Heinz should not steal the medicine because the law prohibits stealing, making it illegal. Or: Heinz should steal the drug for his wife but also take the prescribed punishment for the crime as well as paying the druggist what he is owed. Criminals cannot just run around without regard for the law; actions have consequences.

Stage five (human rights): Heinz should steal the medicine because everyone has a right to choose life, regardless of the law. Or: Heinz should not steal the medicine because the scientist has a right to fair compensation. Even if his wife is sick, it does not make his actions right.

Stage six (universal human ethics): Heinz should steal the medicine, because saving a human life is a more fundamental value than the property rights of another person. Or: Heinz should not steal the medicine, because others may need the medicine just as badly, and their lives are equally significant.

Personally, my decision would rely on universal human ethics. In relation to the research, what is most terrifying is the profound change in moral character in lieu of chronic sleep deprivation. If we remember our sophomore year history, the US has engaged in several immoral military acts in the past, such as the institution of American concentration camps, killing raids in Vietnam, and let’s not forget the numerous cases of sexual abuse and rape of women that occurs at these same military schools were chronic sleep restriction is expected. How responsible chronic sleep deprivation is for influencing these poor choices is unknown, but if each country’s military is chronically sleep deprived and making poor choices of moral fiber……..then if this study is universally true, then we have ourselves a global Armageddon.

Olav Kjellevold Olsen; Ståle Pallesen; Jarle Eid (2010). The Impact of Partial Sleep Deprivation on Moral Reasoning in Military Officers SLEEP, 33 (8), 1086-1090

Yesterday, montegraphia and I spent our usual Sunday night watching a movie. The movie, Temple Grandin, is a biographical documentary about Temple Grandin, the Colorado State University professor with autism, who has transformed the meat industry, and who will, most undoubtedly win a Noble Prize someday (fingers crossed). Comparable to others with autism, Dr. Grandin fixates on objects and not people, due to altered brain connectivity. She even engineered this:

A device used to calm cattle to substitute human hugs for mechanical ones because she hates being touched and interrogated by people. Most amazingly, Dr. Grandin has taken advantage of her mathematically and scientifically-wired brain to create the ideal slaughterhouse. She spent years studying herd behavior in cattle, most notably dissecting “moos,” which vary in intensity and type. Through this careful observation, she designed a slaughterhouse that enabled cattle to guide themselves and follow each other through a curving maze without necessitating human cattle prodders (money saved right there). From there, the cattle continued by themselves into a water dip which removes parasites and then proceeded into the slaughter floor. This floor, Temple decided, needed to be painted with white, solid walls because it was somehow comforting to cattle and therefore, would reduce the need for others to calm the animals immediately before it was stunned (money saved again). Even more advantageously, not stressing the cattle during this process, which would keep cortisol and related stress responses low, would ensure better quality meat.

Aside from Temple’s ingenious design and overcoming the social constraints of autism, we must applaud her for her confidence in a stereotypically male-dominated profession (cattle ranching and science….a double whammy!!).

I am about to begin reading her recent book Animals in Translation which I bought months ago. Expect a book review in the near future. In the meantime, here’s an excerpt.

Over the past four years, I have have read hundreds of papers attempting to elucidate the underlying neurobiology of alcoholism. In the beginning, it was pretty mundane; I simply read papers documenting the effects of binging and chronic use on the “big five” neuromodulatory systems: glutamate, GABA, serotonin, dopamine, and acetycholine. Within the past three years, however, there are numerous papers attributing alcohol’s disruptive effects on glutamatergic, GABA-ergic, dopaminergic, serotonergic, and cholinergic neurotransmission to alterations in hormone release (melatonin, ghrelin, cortisol, growth hormone, leptin, estradiol, testosterone, progesterone, aldosterone, to name a few), gene expression, and neuroanatomical functioning (reward systems, circadian systems, mating systems, visual systems, mood systems, you name it). This four-page table, recently published in an article documenting alterations of gene expression related to synaptic modeling, cell signaling, growth, and death in the nucleus accumbens of chronically-drinking rodents, is an ideal example of this complexity. In case you’re skimming this blog entry (don’t worry, I’m not offended because I do the same!), I repeat: this is ONE TABLE!!!

Yep, I know. Not to be overly pessimistic, because I am actively involved in alcohol research, but it’s studies such as these which truly reveal how fracking difficult it is to treat any type of drug addiction. I doubt that we will ever have one drug or a series of drugs that eradicates all symptoms and predispositions to alcoholism. At this point, it’s more about reducing craving and relapse and sadly, will always be.

Bell, R., Kimpel, M., McClintick, J., Strother, W., Carr, L., Liang, T., Rodd, Z., Mayfield, R., Edenberg, H., & McBride, W. (2009). Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption Pharmacology Biochemistry and Behavior, 94 (1), 131-147 DOI: 10.1016/j.pbb.2009.07.019

In this week’s Journal of Neuroscience, Blue Devil researchers have elucidated the neural mechanisms of song learning in swamp sparrows, conveniently featured on the cover of this week’s journal.

First, there are three different types of songs these birds sing (only done in males, of course, as a courting tactic), which is neurobiologically regulated by the “song system” of the brain; the HVC nucleus of the telencephalon. These three songs include songs learned during adolescence, songs heard during adolescence, and songs sung during adulthood. The relative percentage of each type of song encoding is represented below:

Using electrophysiological techniques, the researchers found that encoding was strongest for the tutorial songs sung or heard during each birds’ juvenile years. Interestingly enough, there was no difference in the encoding frequency between juvenile songs heard and songs sung!!! Overall, juvenile songs were more strongly encoded than adult tunes. This is shockingly different if we compare bird song imprinting with human speech learning. There is clear evidence showing the array of words we recall and subsequently use depends on their previous history of use (i.e. if your sentences are cluttered with fillers such as “like,” then your not going to have a difficult time recalling that word!). Secondly, much of our early juvenile verbiage is dependent upon the quality of social interactions. Though these song sparrows do encode juvenile songs heard and sung, which is a by-product of environmental enrichment, imagine how much more intellectual we would be if we weren’t limited by word use frequency. Perhaps these people would be a bit more intellectual…..

Jonathan F. Prather, Susan Peters, Stephen Nowicki,and Richard Mooney (2010). Persistent Representation of Juvenile Experience in the Adult
Songbird Brain Journal of Neuroscience, 30 (31) : 10.1523/JNEUROSCI.6042-09.2010

I usually watch South Park while eating dinner. Today’s episode from Season 12, which documents the increasing homeless problem in South Park that Kyle believes was due to giving an “ungrateful” homeless person $20, and not the recent housing crash, reminded me of all the episodes in which science is used to resolve South Parkian community problems. Here’s a brief anthology of such wicked hilarious science.

Why homeless people ask for change: they need it to survive!!

The beauties of genetic engineering: Why have one ass when you can have four!!

An extremely dumbed down explanation of natural selection as evidence for evolution

An off-colored physics lesson

When science is needed to save the world

Before there was this (I apologize for the awfulness and increasing popularity of this song)

There was (thankfully) this: Research showing that being in and out of love is physiologically comparable to being “high” and addicted to drugs

Even if the current music industry proclaims otherwise:

This study, published in and featured on NCBI ROFL, astutely describes the physiology of falling in love, being addicted to love, and being withdrawn from love and accurately parallels it with the chronology of drug addiction.

To quote the abstract: “There are no recognized definitions or diagnostic criteria for “love addiction,” but its phenomenology has some similarities to substance dependence: euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focused attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences. Limited animal and human studies suggest that brain regions (e.g., insula, anterior cingulated [ACC], orbitofrontal [OFC]) and neurotransmitters (dopamine) that mediate substance dependence may also be involved with love addiction (as for PG).”

Additionally, similar to drug addiction, there are several documentations of “love gone wrong;” jealousy over love leading to death, such “perpetrators” like OJ and victims like Chris Henry.

This study suggests that there is no specific drug reward center(s) of the brain that discriminates between drug and non-drug rewards, but rather integrates any general reward (food, sex, drugs, exercise) and modulates dopamine release accordingly. I wonder if exercise is an appropriate non-pharmacological treatment for love addiction much like it is in curbing alcohol use as my lab has shown. Though I was unable to find appropriate citations on Google Scholar, I wonder if there exists a co-morbidity between sexual and drug addictions?? This would further suggest of a non-drug specific reward system.In the meantime, perhaps some of the same pharmacological agents used to treat drug addiction (antidepressants, dopamine, and glutamate-specific targets) can suppress and/or prevent pathological love.

Reynaud, M., Karila, L., Blecha, L., & Benyamina, A. (2010). Is Love Passion an Addictive Disorder? The American Journal of Drug and Alcohol Abuse DOI: 10.3109/00952990.2010.495183

A few weeks ago, my lab mates and I were discussing results from our current cocaine-centric experimental protocols, when my lab mate remarked; “Who does cocaine anymore??? That’ so 80′s and early 90′s!”

Much like these:

Neo-drugs of abuse today include methamphetamines, X, and any other stimulant designed to extend wakefulness and improve cognitive performance in today’s every-increasing high-pressure, information-overload society. Read the awesome blog Drug Monkey for more info on these drugs’ prevalence of use and abuse.

In support of “cocaine….that’s so 80s” hypothesis, a recent paper in PLoS highlighted the weak addictive potential of cocaine relative to other rewards, particularly non-drugs rewards such as sweets. Hypersensitization (i.e. highly active animal and cascades of excitatory neurotransmitter release), a hallmark of cocaine use, often overestimates the currently thought rewarding and addictive properties of this drug, resulting in cocaine to rank higher on ladder rung of addictive drugs.

Using a procedural ratio task (must increasingly work (i.e. lever press) for a reward) and subsequent extinction (i.e. a period in which repeated lever presses will not elicit a reward; see previous post) and choice-preference (equal opportunity to obtain one of two rewards), the project researchers found the following.

First, the rats will more quickly lever press for a cocaine reward (breaking point) and will subsequently administer more cocaine relative to taste of sweetened (uncaloric) water. This is show here.

To assess whether this hyper-responding to cocaine was due to its addictive potential or simply was an artifact of cocaine’s stimulating properties (just can’t help being active), the researchers extended the latency to which a lever press would elicit a reward from immediately to 10-minutes. Turns out, that the rats were more willing to work for the sweetened-solution over cocaine under this circumstance.

And lever-pressing was more prolonged during extinction (an indication of habit-forming behavior) in the sweet-treated group.

This was secondarily supported by evidence that in a free-choice task, the rats preferred the sweetened-water more often than cocaine. This effect was further potentiated if the animals were food-restricted and were given the choice between cocaine and a sweet (caloric) solution.

Lastly, and most interestingly, animals that chronically received excessively high doses of cocaine (up to 468 mg, which is the human equivalent of about 750 grams or 214 eight-balls!!!!), still have a moderately low-preference and responding for cocaine over sweet solutions.

Though this research slightly undermines the current hypotheses of drug addiction research, it certainly explains an animal’s biologically-wired inclination to crave sweets, and therefore, definitely contributes to obesity-related research.

Lauriane Cantin, Magalie Lenoir, Eric Augier, Nathalie Vanhille, Sarah Dubreucq, Fuschia Serre, Caroline Vouillac, Serge H. Ahmed (2010). Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction PLoS , 5 (7) : 10.1371/journal.pone.0011592

I’ve been anticipating the release of Inception since I saw a movie preview for it six months ago. Even more exciting, the public has taken great interest in the subject of sleep and dreaming as evidenced by the numerous interviews conducted with sleep and dream experts the past few weeks. The movie received a horrific review in The New Yorker, a magazine that I typically rely on to decide whether or not to see a movie, even if the preview (per usual) seems enticing, but I’m glad I didn’t listen. After all, a 2.5 hr movie revolving around the dissection of dreaming and the unconscious is extremely exciting for a nerd like me.

To familiarize yourself with the plot, here’s the official trailer.

Now, for a few comments. The actions of the characters within the movie truly adhere to the properties of a dream (i.e. Christopher Nolan and the other writers did their research). For example: 1) They abided by the idea that dreams never seem strange while occurring (defying gravity, walking on water, climbing up buildings), but they do upon awakening. This feeling of strangeness alerts the dreamer that “it was just a dream;” 2) Dream time proceeds much more slowly than real time. Think about it. The average amount of time a dreamer spends in REM sleep, the stereotypical sleep stage of dreaming, is 15-25 min in a 90-min sleep cycle across the night. Then why is it that some dreams appear to last hours, if not days? In Inception, the main dream (and plot) was comprised of three levels (i.e. the dreamer realizing that he was dreaming and then entering the dreams of another dreamer) with the first level progressing 20 times slower than real-time (dreamer dreaming), the second level (the dreamer realizing that he is dreaming) progressing 20 times slower than the first, and the third level (the dreamer who realizes he is dreaming enters the dream of another dream character) progressing 20 times slower than the second. I can’t imagine a fourth-dimension dream, but I assure you it’s possible.

For more insights into the properties of the dreaming world, check out my second blog post on Dormivigilia 1.5 years ago which details such properties.

Dream on!!

First off, I would like to acknowledge that this is the first time in months that I am publishing Neury Thursday on time (clearly indicative of animals entraining and little experimenting). Secondly, I would like to acknowledge that for the first-time in my graduate career, there are at least two articles in each of this week’s high-impact publications (Nature, Science, and Journal of Neuroscience) regarding circadian biology!!!

Given the central theme of this week’s Neury Thursday, I feel inclined to provide a prelude because the only reason you can enjoy “Harold and Kumar Go To White Castle” is if you are activating your cannabinoid receptors, as discussed here:

This week’s Neury Thursday article is of great interest to me because: 1) it elucidates the direct effect’s of abused drugs on the circadian pacemaker and behavioral entrainment (the central theme of my dissertation); 2) it enthusiastically increases awareness about a highly under-represented receptor type involved with addiction, cannabinoid receptors (appropriately named, don’t you think???); and 3) the authors took a viable human experience, being on “pot time,” and like most nerds, yearned to disentangle the underlying neurobiology of this phenomenon, which logically, must involve disruption to an internal clock.

Using electrophysiological, immunological, and behavioral techniques, Eli and Buckeye researchers discovered that infusions of WIN55, a cannabinoid receptor agonist (i.e. pot), into the lateral ventricle greatly reduced light-induced delays of behavioral rhythms. This effect was partially reversed by the co-infusion of a cannabinoid antagonist, which when administered alone, also produced a modest delay in rodents’ rhythms/wake up times.

These are the activity records showing pot attenuation of behavioral rhythm delays.

To mechanistically understand why this pot attenuation occurs, the researchers first localized cannabinoid receptors in the circadian pacemaker and found high expression in the dorsalateral regions (typically referred to as the shell) as shown here.

Using patch clamp techniques, the researchers observed that the application of the cannabinoid agonist dramatically increased the firing rate of neurons (a rather juxtaposing effect to the human perception of pot’s physiological effects). Using pharmacology, the researchers then uncovered that cannabinoid agonists hyperexcite clock neurons by means of reducing inhibitory GABA activity on presynaptic neurons.

Interestingly, cannabinoid attenuation of behavioral circadian responses is not dissimilar from my research findings with alcohol. Both appear to act through GABA receptors within the SCN to disrupt (attenuate) circadian timing, though alcohol appears to act extrasynaptically (think glial cells) and not presynaptically. This work was done by Rebecca Prosser and her undergraduates at the University of Tennessee.

More importantly, the broad effects that these drugs appear to have on neuronal function and behavioral output reveal how easy it is to crave and become addicted to drugs and how difficult it is, once addicted, to come clean.

Claudio Acuna-Goycolea, Karl Obrietan, and Anthony N. van den Pol (2010). Cannabinoids Excite Circadian Clock Neurons Journal of Neuroscience, 30 (30), 10061-10066 : 10.1523/JNEUROSCI.5838-09.2010

McElroy B, Zakaria A, Glass JD, & Prosser RA (2009). Ethanol modulates mammalian circadian clock phase resetting through extrasynaptic GABA receptor activation. Neuroscience, 164 (2), 842-8 PMID: 19695310

Over the past ten days, I have been chillaxing in Fort Myers, Florida and the surrounding area with my mom’s family for the 1st Annual Evanoff (my mom’s maiden name) Extravaganza. The week was booked with numerous festivities beginning as early as 4 AM (four hour travel to Universal Studios) and as late at 2 AM (traveling 20 miles south to a club only to discover that my brother and other male cousins could not enter because they were wearing shorts!!!!!).

These pictures from Universal Studios in Orlando, my high school BFF’s wedding to the person of her dreams since 7th grade (!!!), and Evanoff cuckoo and craziness capture my two week blogging hiatus, which will be no more that is if I don’t travel to the remote land of Costa Rica again…..wishful thinking……

From A Day At Hogwarts, Robyn’s Wedding, and Evanoff Extravanganza, posted by Allison Brager on 7/28/2010 (50 items)

Generated by Facebook Photo Fetcher