Exploring the role of dopamine in cocaine abuse

2015

Challenge

It is almost impossible to determine which individuals have a higher biological risk for addiction to cocaine and other stimulants. But, in some individuals, cravings correlate with high levels of dopamine, and those levels can be increased even further simply by visualizing drug-associated cues. Similarly, low levels of available dopamine D2 receptors are often seen in cocaine-users, but whether low receptor levels are a cause or consequence of stimulant dependence was unclear. 

Advance

IRP researchers led by Veronica A. Alvarez, Ph.D., addressed the challenge using a newly available transgenic mouse model with selective deletion of dopamine D2 receptors in the same neurons that release dopamine into the forebrain—autoreceptors that provide negative feedback regulation over dopamine release. They discovered that a reduction in D2 autoreceptors enhanced the likelihood that mice would engage in cocaine use, which also made them more vulnerable to cocaine in an animal model of relapse.

Impact

Identifying a low level of dopamine D2 receptors as a potential vulnerability factor in the development of addictive behaviors is an important step towards the implementation of drug abuse prevention strategies. Additionally, this work contributes to a body of research that is demonstrating the value of animal models in behavioral science.

Publications

Holroyd KB, Adrover MF, Fuino RL, Bock R, Kaplan AR, Gremel CM, Rubinstein M, Alvarez VA. (2015). Loss of feedback inhibition via D2 autoreceptors enhances acquisition of cocaine taking and reactivity to drug-paired cues. Neuropsychopharmacology. 40(6):1495-509.

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