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Addictive drugs refer to some prescription drugs commonly used clinically for anesthesia, analgesia, anti-anxiety, and anti-depression
.
These drugs have good curative effects when used rationally under the guidance of doctors, but excessive use can cause euphoria, and continuous use can cause severe physical and psychological dependence.
Stopping the drug can lead to physical dysfunction and withdrawal.
Symptoms
.
The dopamine (DA) system in the brain is a key neural substrate for drug addiction, especially the DA pathways of the mesencephalon and mesorrstria that control the nucleus accumbens (NAc) and dorsal striatum (DSt)
.
These two striatal regions have different incoming and outgoing connections, participate in unique behavioral functions and are regulated by drug abuse
.
Some previous neuroimaging studies have shown that repeated long-term exposure to cocaine is associated with decreased availability of striatal dopamine 2 receptors (D2R), while low availability of striatal D2R is associated with increased cocaine intake
.
These findings indicate that D2Rs are key regulators of motivational behavior, and that changes in their level and availability are tools for cocaine-induced behavioral adaptation
.
However, the specific mechanism by which cocaine may regulate D2R is still unclear
.
On September 9, 2021, a research team from Colorado Anschutz School of Medicine and Case Western Reserve University School of Medicine published an article titled "Cocaine Shifts dopamine D2receptor sensitivity to gate conditioned behaviors" in Neuron.
It was found that cocaine can dynamically regulate the expression of G protein and thus affect the sensitivity of D2 receptors
.
Document DOI: https://hub.
pubmedplus.
com/10.
1016/j.
neuron.
2021.
08.
012 First, in order to study the effect of cocaine exposure in vivo on D2R sensitivity, researchers injected cocaine into mice and observed the small Changes in rat status
.
Experiments have shown that: cocaine exposure can selectively reduce the sensitivity of D2Rs temporarily, and after a long period of withdrawal, the sensitivity can be restored by re-exposing to cocaine
.
The researchers then changed the expression level of D2R in the striatum to see if reducing or increasing receptor levels would block the effects of cocaine
.
Experiments have shown that in mice with D2R knockout and overexpression, the sensitivity of D2R has not changed, and both still show a decrease in selectivity
.
These results all indicate that cocaine can reduce the sensitivity of D2R in NAc, but changing the level of D2R cannot prevent the change in sensitivity caused by cocaine
.
Subsequently, the researchers conducted a more in-depth mechanism study on the above phenomenon, focusing on exploring the potential mechanism of whether repeated exposure to cocaine could reduce the selective sensitivity of D2Rs by differentially regulating the Gα protein level in this region
.
WB experiments showed that acute cocaine did not affect the high protein and Gα protein levels of NAc and DSt, while chronic cocaine exposure selectively reduced the high protein level of NAc without changing the high protein level of DSt
.
Further experiments also proved that long-term exposure to cocaine initially modulates the sensitivity of D2R signals by changing the preferential coupling with G protein, rather than changing the overall level of D2R expression
.
Finally, the researchers explored the relationship between changes in D2R sensitivity and addictive behaviors caused by cocaine exposure
.
A series of behavioral studies using cocaine self-administration, conditional spatial preference, and behavioral sensitization studies have found that the decrease in D2 receptor sensitivity caused by psychostimulants drives cocaine seeking behavior, indicating that it changes D2 receptor sensitivity The change is sufficient to cause specific addictive behaviors caused by cocaine exposure
.
Experimental mechanism diagram In summary, this article describes how cocaine exposure can selectively reduce the sensitivity of D2Rs instead of expression to change dopamine signaling by changing the relative expression and coupling of G protein subunits
.
Cocaine-induced reduction in D2R sensitivity promotes the development of cocaine's reward effect, because blocking the reduction in G protein expression is sufficient to prevent cocaine-induced behavioral adaptation
.
In order to facilitate you to continue to receive our articles, you are welcome to set us as a "star" so that you can see our news in the future
.
End reference materials: [1]https://
.
These drugs have good curative effects when used rationally under the guidance of doctors, but excessive use can cause euphoria, and continuous use can cause severe physical and psychological dependence.
Stopping the drug can lead to physical dysfunction and withdrawal.
Symptoms
.
The dopamine (DA) system in the brain is a key neural substrate for drug addiction, especially the DA pathways of the mesencephalon and mesorrstria that control the nucleus accumbens (NAc) and dorsal striatum (DSt)
.
These two striatal regions have different incoming and outgoing connections, participate in unique behavioral functions and are regulated by drug abuse
.
Some previous neuroimaging studies have shown that repeated long-term exposure to cocaine is associated with decreased availability of striatal dopamine 2 receptors (D2R), while low availability of striatal D2R is associated with increased cocaine intake
.
These findings indicate that D2Rs are key regulators of motivational behavior, and that changes in their level and availability are tools for cocaine-induced behavioral adaptation
.
However, the specific mechanism by which cocaine may regulate D2R is still unclear
.
On September 9, 2021, a research team from Colorado Anschutz School of Medicine and Case Western Reserve University School of Medicine published an article titled "Cocaine Shifts dopamine D2receptor sensitivity to gate conditioned behaviors" in Neuron.
It was found that cocaine can dynamically regulate the expression of G protein and thus affect the sensitivity of D2 receptors
.
Document DOI: https://hub.
pubmedplus.
com/10.
1016/j.
neuron.
2021.
08.
012 First, in order to study the effect of cocaine exposure in vivo on D2R sensitivity, researchers injected cocaine into mice and observed the small Changes in rat status
.
Experiments have shown that: cocaine exposure can selectively reduce the sensitivity of D2Rs temporarily, and after a long period of withdrawal, the sensitivity can be restored by re-exposing to cocaine
.
The researchers then changed the expression level of D2R in the striatum to see if reducing or increasing receptor levels would block the effects of cocaine
.
Experiments have shown that in mice with D2R knockout and overexpression, the sensitivity of D2R has not changed, and both still show a decrease in selectivity
.
These results all indicate that cocaine can reduce the sensitivity of D2R in NAc, but changing the level of D2R cannot prevent the change in sensitivity caused by cocaine
.
Subsequently, the researchers conducted a more in-depth mechanism study on the above phenomenon, focusing on exploring the potential mechanism of whether repeated exposure to cocaine could reduce the selective sensitivity of D2Rs by differentially regulating the Gα protein level in this region
.
WB experiments showed that acute cocaine did not affect the high protein and Gα protein levels of NAc and DSt, while chronic cocaine exposure selectively reduced the high protein level of NAc without changing the high protein level of DSt
.
Further experiments also proved that long-term exposure to cocaine initially modulates the sensitivity of D2R signals by changing the preferential coupling with G protein, rather than changing the overall level of D2R expression
.
Finally, the researchers explored the relationship between changes in D2R sensitivity and addictive behaviors caused by cocaine exposure
.
A series of behavioral studies using cocaine self-administration, conditional spatial preference, and behavioral sensitization studies have found that the decrease in D2 receptor sensitivity caused by psychostimulants drives cocaine seeking behavior, indicating that it changes D2 receptor sensitivity The change is sufficient to cause specific addictive behaviors caused by cocaine exposure
.
Experimental mechanism diagram In summary, this article describes how cocaine exposure can selectively reduce the sensitivity of D2Rs instead of expression to change dopamine signaling by changing the relative expression and coupling of G protein subunits
.
Cocaine-induced reduction in D2R sensitivity promotes the development of cocaine's reward effect, because blocking the reduction in G protein expression is sufficient to prevent cocaine-induced behavioral adaptation
.
In order to facilitate you to continue to receive our articles, you are welcome to set us as a "star" so that you can see our news in the future
.
End reference materials: [1]https://
