STUDIES: Why It’s So Hard To Quit Cocaine & Cocaine Makes Brain Cell Cannibalize Themselves

Editor’s Note:  We recently published an article about 2 North Lake Tahoe bartenders who have been arrested and charged with selling cocaine to customers.  Cocaine use is certainly an issue in Lake Tahoe and many ski towns in North America.  It only makes sense to have all the latest information on what researchers know about what cocaine does to the human brain.

“We discovered that one single shot of cocaine can completely change the brain architecture and set up an addict for relapse.” – Lead researcher Dr Peter McCormick, from University of East Anglia, Enland’s School of Pharmacy

A recent study conducted by a team of researchers at Bordeaux University revealed that cocaine induces a long-lasting remodeling of brain cell connections which alters the brain’s sensitivity to future doses of the drug.  The findings of the study provided new information about how continuous use of the drug leads to increased tolerance and desensitization, and new methods to allow addicts to erase their drug-seeking tendencies.

Another recent study published in the National Acadamey of Sciences suggests that cocaine makes brain cells eat themselves, a process called autophagy.

“A cell is like a household that is constantly generating trash.  Autophagy is the housekeeper that takes out the trash — it’s usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell.” – Prasun Guha, Ph.D., postdoctoral fellow at Johns Hopkins and lead author of the paper

The ventral subiculum ventral (vSUB), which is part of brain’s hippocampus, is stimulated by the drug and the dopamine neurons in the ventral tegmental area (VTA) are altered into a hyperactive state. This increases the brain’s sensitivity to subsequently low doses of cocaine for a period of at least five days afterwards. The vSUB has been labeled the“addiction centre” due to previous association with generation of drug-seeking impulses in response to external cues. Prior to this study, the mechanisms by which it drives this behavior were unknown.

Speaking to IFLScience, study coauthor Francois Georges explained that the results of the experiment are significant since they have helped to finally identify “a neuronal circuit that for sure is changed during cocaine administration.”

The team of researchers at Bordeaux University conducted the study by activating the vSUB of a number of rats using a method called high frequency stimulation, which involves stimulating the synapses, connections between neurons, with bipolar electrical currents. This method produces the same effects that a high dose of cocaine would. The conductors of the study monitored the neuronal activity that was produced by the stimulation, which prompted them to notice that that the vSUB increased the responsiveness of the VTA dopamine neurons by relaying messages through a region called the bed nucleus of the stria termilanil (BNST). The rats showed increased behavioral responses to “sub-threshold’ doses of the drug, which are smaller doses that wouldn’t normally provoke a reaction.

“By synaptic stimulation we were able to change the plasticity of the dopaminergic neurons. Through this stimulation we put the brain into a phase where it becomes more receptive to low doses of cocaine. It’s like we prepared the brain to be more responsive to the drug,” explains Georges.

This study provides information about how the neural circuits by which single doses of cocaine alter sensitivity to future doses of the drug, and could lead to a new understanding of how prolonged cocaine use ultimately causes desensitization, but more research is needed to determine precisely how this occurs. If these findings are to be used for therapeutic use, further work is required, since, as Georges explains, “what we found is a way to make cocaine more potent, which is not what you want if you want to treat addiction.” For researchers that are seeking to reverse the effects of cocaine, the fact that the neuronal pathways involved in altering sensitivity to cocaine have now been identified provides them with a great starting point.

“The idea now would be to manipulate this circuit to see if we can reduce the effect of cocaine, which could be a lead to decrease cocaine intake in drug addicts,” says Georges.