Dopamine, Fruit Flies, Masochism, and Lethargy


According to this arstechnica article fruit flies lacking (or with extremely low levels of) dopamine suffer from extreme lethargy, and a type of masochism!

Flies that apparently lack dopamine signaling manage to live just as long as their peers. They do, however, end up turning into lethargic masochists. [...]

However, they’re nowhere close to normal. Compared to their normal peers, they were very lethargic, moving relatively little through the course of their normal lives, and not expending the effort to move out of the path of a mild electric current. They spent a lot of their time in the fly equivalent of sleep, even during daylight hours, when they are normally active. Despite the lethargy, however, caffeine was still able to give them a kick start, suggesting that there’s an intact activity control that is simply not getting the sorts of cues it needs without dopamine around.

The same sorts of issues showed up when feeding and visual activity were tested. The flies that lacked dopamine ate only about a third as much as their normal peers and weren’t interested in sugar water even after having been starved. They were still able to respond to sugar and eat, however, which suggests that the animals’ brains still have a feeding capacity that ends up going unused without dopamine. The flies also had normal vision and could use it for spatial orientation, but would no longer move towards light (a phenomenon called phototaxis).

The weirdest effect, however, came when the flies were tested for learned aversion, in which an electric shock is associated with a particular odor. Instead of learning to avoid the shock, however, the dopamine-deficient Drosophila ended up being attracted to the odor, hence the authors’ use of the term “masochistic” to describe the flies’ behavior. (via.)


Morphine & brain testosterone levels


A single injection of morphine to fight persistent pain in male rats is able to strongly reduce the hormone testosterone in the brain and plasma [...] The study, led by Anna Maria Aloisi, M.D., showed that opioids had “long lasting genomic effects in body areas which contribute to strong central and peripheral testosterone levels” including the brain, the liver and the testis.

The study showed increases in aromatase, an enzyme that is responsible for a key step in the biosynthesis of estrogen. The findings are particularly important since testosterone is the main substrate of aromatase, which is involved in the formation of estradiol. [...]

Opioid induced hypogonadism can cause health complications to which patients with pain can be overly susceptible, including chronic fatigue, loss of stamina, emotional and sexual disturbances, as well painful skeletal and muscular complications. [...]

“Until a few years ago this condition was completely unrecognized by physicians although some reports clearly showed it in many kinds of patients,” notes Dr. Aloisi. (via.)

This is interesting, because it’s also been demonstrated that chronically anxious rat phenotypes have fewer steroid receptors (testosterone being a steroid, of course) in their brains. Additionally, exercise was one of the only things capable of reversing this phenotype. Exercise causes a rush of endorphins after training, which activate the same receptors (mu opioid) as morphine.


Increased Anterior Cingulate Cortex & Somatosensory Cortex Activation Involved in Hyperalgesia


Using magnetic resonance imaging (MRI) to assess brain function, Coghill and colleagues found that study participants who said that a heat stimulus was intensely painful had pronounced activation of brain regions that are important in pain. In contrast, people who said that the same stimulus was only mildly painful had minimal activation of these same areas.

“One of the most difficult aspects of treating pain has been having confidence in the accuracy of patients’ self-reports of pain,” said Coghill, an assistant professor of neurobiology and anatomy. “These findings confirm that self-reports of pain intensity are highly correlated to brain activation and that self-reports should guide treatment of pain.”

For the research, 17 normal, healthy volunteers (eight women and nine men) had a computer-controlled heat stimulator placed on their leg. While their brains were scanned, this device heated a small patch of their skin to 120° Fahrenheit, a temperature that most people find painful. However, participants reported very different experiences of pain. Using a 10-point scale, the least sensitive person rated the pain around a “one,” while the most sensitive person rated the pain as almost a “nine.”

People who reported higher levels of pain showed increased activation in areas of the brain important in pain: the primary somatosensory cortex, which contributes to the perception of where a painful stimulus is located on the body and how intense it is, and the anterior cingulate cortex, which is involved in the processing the unpleasant feelings evoked by pain. However, there was little difference between subjects in activation of the thalamus, which is involved in transmitting pain signals from the spinal cord to higher brain regions.

“This difference between cortical and thalamic patterns of activation may help explain pain differences between individuals,” said Coghill. “This finding raises the intriguing possibility that incoming painful information is processed by the spinal cord in a generally similar manner. But, once the brain gets involved, the experience becomes very different from one individual to the next.”

Coghill believes that most individual differences in pain sensitivity are probably due to a combination of cognitive factors, such as past experience with pain, emotional state at the time pain is experienced, and expectations about pain. (via.)


Modulation of pain via neurofeedback of rostral anterior cingulate cortex


Twenty years ago Rosenfeld found that he could change the pain threshold in mice by training them to alter their brainwave patterns through a process called conditioned learning, where an altered brainwave state was rewarded by direct stimulation of the reward centres in their brains. Since this meant placing an electrode into the brain, however, his team never tried the technique on people.

Now Fumiko Maeda, Christopher deCharms and their colleagues at Stanford University in California have tried showing people real-time feedback from a functional magnetic resonance imaging (fMRI) scanner.

The difference between EEGs and fMRI, says Rosenfeld, is that fMRI allows you to show volunteers how much activity there is in specific areas of their brains. “From scalp recordings, you don’t really know what you are recording,” he says.

The eight volunteers saw the activity of a pain-control region called the rostral anterior cingulate cortex represented on a screen either as a flame that varied in size, or as a simple scrolling bar graph.

This brain region is known to modulate both the intensity and the emotional impact of pain. During the scans the volunteers had to endure painful heat on the palm of their hand. They were asked to try to increase or decrease the signal from the brain scanner and to periodically rate their pain sensations.

It took just three 13-minute sessions in the scanner for the eight volunteers to learn to vary the brain activity level, and thus to develop some control over their pain sensations, the researchers reported at the Cognitive Neuroscience Society meeting in San Francisco last week.

The effect seemed to last beyond the sessions in the scanner, although the researchers have yet to determine how strongly and for how long. The volunteers could not explain how they did it. The researchers ruled out other explanations for the effect through a series of controls. They gave people false feedback data, no feedback at all, or feedback from a part of the brain unrelated to pain control. They also sometimes asked people to pay attention to the pain or distracted their attention away from it. (via.)


Broddman Area 25 (ACC) & Sadness/Crying


Mayberg, for instance, asks volunteers to recall a sad memory. When they start crying, she uses a PET scan to measure blood flow in the brain. The “hottest” area (the one with the biggest increase in blood flow) turns out to be a small part of the anterior cingulate called area 25, part of the limbic system. While this area gets more active, the prefrontal cortex, or thinking area, turns off.

In healthy people immersed in sad feelings, the brain can quickly shift back toward equilibrium. “The phone rings, the baby cries, the boss calls and you immediately disengage from the sadness and the thinking part of the brain turns back on,” she says. With depressed people, this ability to shift back to equilibrium is altered. (via: dynorphin and depression)


Relief of scratching an itch reduces Anterior Cingulate Cortex activation


“To our surprise, we found that areas of the brain associated with unpleasant or aversive emotions and memories became significantly less active during the scratching,” said Yosipovitch. “We know scratching is pleasurable, but we haven’t known why. It’s possible that scratching may suppress the emotional components of itch and bring about its relief.”

The reduced brain activity occurred in the anterior cingulate cortex, an area associated with aversion to unpleasant sensory experiences, and the posterior cingulate cortex, which is associated with memory. When participants reported that the scratching felt most intense, activation in these areas was lowest.

Yosipovitch said patients occasionally report that intense scratching – to the point of drawing blood – is the only thing that relieves chronic itch.

“This is the first real scientific evidence showing that itch may be inhibited by scratching,” he said. “Of course, scratching is not recommended because it can damage the skin. But understanding how the process works could lead to new treatments. For example, drugs that deactivate this part of the brain might be effective.” (via.)