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Mental fatigue impairs midbrain function in cocaine-addicted individuals, researchers

Jabberwocky

Frumious Bandersnatch
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(Medical Xpress)?Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have revealed a new connection between drug addiction and a distinct part of the brain that may govern motivation. The research, published October 23, 2012, in Translational Psychiatry as an Advance Online Publication, shows that individuals addicted to cocaine have abnormal functioning of the midbrain, a brain region responsible for releasing dopamine in the presence of important stimuli, such as food, to make individuals repeat the behaviors that would result in obtaining these stimuli again.

The study sought to highlight how the midbrain operates in cocaine-addicted individuals when fatigue sets in. Using functional magnetic resonance imaging (fMRI), a way of noninvasively mapping brain function, scientists recorded both healthy individuals' and cocaine-addicted individuals' midbrain activity throughout the course of a classic test of mental acuity with the intention of imposing fatigue through task repetition. Called the Stroop test, the task involves indentifying the color of the letters of a word that spell out the name of the same or a different color. Because a faster response is to read a word than identify its color, the test measures one's ability to inhibit a dominant, but incorrect, response when for example the word blue is written in red ink.

Scientists posited that as the test neared its end and the subjects' fatigue was higher, the midbrain would be more active. As recent evidence has shown that the midbrain might also be strongly tied to motivation, scientists theorized that higher activity in the midbrain provides a boost to keep individuals motivated.

"When the healthy controls activated this region as they presumably became fatigued, we interpreted it to mean they were getting a bump in motivation," said lead author Scott J. Moeller, a postdoctoral fellow at Brookhaven Lab. "The cocaine users showed an opposite pattern?midbrain activity actually decreased over the course of the task," he said.

The study rests on the idea that when you suffer from addiction, fatigue?whether from a difficult task or mental stress from a long day?could make you more susceptible to your harmful indulgences. "If you're stressed or tired, you might go for that chocolate that you might not have gone for otherwise," Moeller said of even healthy individuals when faced with an indulgence. "The stakes are higher for individuals addicted to cocaine."

Once the connections between fatigue and midbrain activity were established, the team set out to reverse the effects in the addicted individuals using pharmaceuticals.

"We know that drug addiction is associated with many deficits in dopamine function," Moeller said. So in a new group of addicted individuals the scientists administered methylphenidate, which boosts the amount of dopamine in the brain, during one study session while administering a placebo during another study session. When given placebo, the researchers saw no change in subjects' midbrain activity; when given methylphenidate, however, the researchers saw exactly what they were looking for.

"When they were given methylphenidate, the cocaine-addicted subjects started to look more like the controls in how their midbrain functioned during fatigue."

In contrast, "the controls who were given methylphenidate actually started to look like the cocaine subjects?it was a complete flip," Moeller said, explaining that in the healthy control group, too much dopamine can degrade cognitive functioning.

Though the study was only one in a series of investigations, potential applications of the results down the line could yield new, highly effective methods of drug rehabilitation.

"If certain drugs can be shown to enhance functioning of this brain region, then maybe we can use it in service of sustaining addicted individuals' motivation in situations that might otherwise trigger relapse," he said.


Source: https://medicalxpress.com/news/2012-11-mental-fatigue-impairs-midbrain-function.html
 
Very interesting! Thanks for this noonoo :)

How wonderful would it be to have a more effective modality to enhance cocaine use disorder recovery!
 
Striatal dopamine levels seem a high value target in understanding addiction.

Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents.
Thanos PK1, Michaelides M, Benveniste H, Wang GJ, Volkow ND.

1
Behavioral Neuropharmacology and NeuroImaging Lab, Medical Department, Building 490, Brookhaven National Laboratory, Upton, NY 11973-5000, United States. [email protected]
Abstract
BACKGROUND:
Methylphenidate (MP) and amphetamine, which are the mainstay for the treatment of ADHD, have raised concerns because of their reinforcing effects and the fear that their chronic use during childhood or adolescence could induce changes in the brain that could facilitate drug abuse in adulthood.
METHODS:
Here we measured the effects of chronic treatment (8 months) with oral MP (1 or 2 mg/kg), which was initiated in periadolescent rats (postnatal day 30). Following this treatment, rats were tested on cocaine self-administration. In addition at 2 and 8 months of treatment we measured dopamine D2 receptor (D2R) availability in the striatum using [(11)C]raclopride microPET (microPET) imaging.
RESULTS:
Animals treated for 8 months with 2 mg/kg of MP showed significantly reduced rates of cocaine self-administration at adulthood than vehicle treated rats. D2R availability in the striatum was significantly lower in rats after 2 months of treatment with MP (1 and 2 mg/kg) but significantly higher after 8 months of MP treatment than in the vehicle treated rats. In vehicle treated rats D2R availability decreased with age whereas it increased in rats treated with MP. Because low D2R levels in the striatum are associated with a propensity for self-administration of drugs both in laboratory animals and in humans, this effect could underlie the lower rates of cocaine self-administration observed in the rats given 8 months of treatment with MP.
CONCLUSIONS:
Eight month treatment with oral MP beginning in adolescence decreased cocaine-self administration (1 mg/kg) during adulthood which could reflect the increases in D2R availability observed at this life stage since D2R increases are associated with reduced propensity for cocaine self administration. In contrast, two month treatment with MP started also at adolescence decreased D2R availability, which could raise concern that at this life stage short treatments could possibly increase vulnerability to drug abuse during adulthood. These findings indicate that MP effects on D2R expression in the striatum are sensitive not only to length of treatment but also to the developmental stage at which treatment is given. Future studies evaluating the effects of different lengths of treatment on drug self-administration are required to assess optimal duration of treatment regimes to minimize adverse effects on the propensity for drug self administration.
PMID: 17599397 DOI: 10.1016/j.pbb.2007.05.020

https://www.ncbi.nlm.nih.gov/pubmed/17599397
 
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