Cocaine, Electric Shock and Friendly Viruses

One of the most devastating aspects of substance use disorder is the loss of control over drug seeking and use.  Scientists have hypothesized that the reduced volume and activity of the brain area responsible for decision-making and inhibitory control, prefrontal cortex (PFC), could contribute to the reported loss of control.  In order to test this hypothesis and determine if the effects could be reversed Chen and his colleagues at NIDA developed an animal model of compulsive drug seeking in which following a long history of drug self-administration some rats would continue to take cocaine even when it was followed by an electric shock. These rats were termed "shock-resistant", while the rats that stopped using cocaine were termed "shock-sensitive".  

Foot shock reduced drug seeking 

in the shock-sensitive rats, but not 

the shock-resistant rats.

Following the behavioral part of the experiment, the rats’ brains were removed and tested to determine if the PFC of the shock-resistant rats was different from that of the shock-sensitive rats.  The scientists found that the neurons of the shock-resistant rats required twice as much current as the other rats in order to fire.  Their PFC was said to be "hyposensitive". This suggests that after the rat had been shocked his PFC didn't fire enough to inhibit future drug seeking. To determine if the effects of cocaine on the PFC could be reversed, rats were injected with virus that encoded for a light sensitive protein, a process called optogenetics. The neurons of the PFC were infected with the virus and therefor forced to produce the light sensitive protein.  Fiber optic cables were then implanted in rats’ brains. When the light was turned on the PFC was stimulated

through the activation of the light-sensitive proteins. This procedure allowed scientist to selectively activate areas of the PFC. As predicted, when the light was turned on giving the PFC a boost of activity, rats were able to resist cocaine seeking.  These finding suggest that at least for individuals who want to inhibit drug seeking behavior it is possible to reverse the effects of drug use on the inhibitory centers of the brain.  An individual who previously felt a complete loss of control over drug seeking could artificially boost his "self-control" with the touch of a button.  One of the limitations of this study is that like all animal models it cannot completely mimic all aspects of a drug use disorder in humans.  It has however demonstrated a biological basis for the loss of control that characterizes so many individuals with substance use disorders and offered hope for a possible treatment.  

Chen BT, Yau HJ, Hatch C, Kusumoto-Yoshida I, Cho SL, Hopf FW, & Bonci A. (2013). Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature. 496(7445), 359-62.

 Abstract