The "Back Door" to Cocaine Addiction

The "Back Door" to Cocaine Addiction 

Addiction is a condition that can cause some of the ugliest behaviors possible. It takes many forms and can be associated with a multitude of activities. For a long time there has been a misconception about addiction. People have always associated addiction as a problem with the conscious thinking. People addicted to online shopping, gambling, and drugs would be stigmatized as people with poor self-control. However, this might not necessarily be the case. Dr. Daniel McGehee came to Loyola and gave a talk on related to the topic of addiction. It is well known in the scientific community that persistent alterations to synaptic activity in the ventral tegmental area (VTA) contribute to addictive behaviors. That means repeated exposure of drugs, like cocaine, affect the brain in that more synaptic connections are created which enhance the elevated feeling that people get when on this stimulant. Dr. McGehee looked to define the molecular mechanisms that specifically related to increased synaptic activity. 

He researched the effects of cocaine on brain slices of young rats with no previous exposure to these drugs. Acute exposure to these drugs resulted in long term potentiation at excitatory synapses on VTA neurons. Long term potentiation is basically repeated exposure to a molecule that results in long lasting effects. In this case, the repeated exposure to cocaine resulted in long lasting effects on AMPAR/NMDAR receptor ratios. These receptors are located on dopamine neurons in the VTA. An increase in receptors on the dopamine neurons results in a higher probability of cocaine to bind to those receptors. Once the drug binds, that causes more dopamine to be synthesized and leads to a reliance on higher levels of dopamine which results in addiction. 

Another article, "Cocaine addiction: Scientists discover 'back door' into the brain", talks about cocaine addiction and the results of various experiments that have shed light providing a deeper understanding of addiction. Previous research conducted by Professor Barry Everitt showed that when rats would self administer cocaine they experienced activity in their nucleus accumbens, which plays an important role in "goal directed" behavior. This is affected short-term behavior. When rats were given cocaine for an extended period of time, the activity transferred to the dorsolateral striatum, which is important in habitual behavior. This affected long-term behavior and suggests that the rats had no control and were just responding automatically to their new drug taking habit. 

This article then presented a drug used to overcome cocaine addiction. Once rats were exposed to N-acetylcysteine they lost their motivation to self-administer cocaine. This is an important finding because earlier Everitt demonstrated how repeated exposure to cocaine resulted in a loss of control in

cocaine intake. N-acetylcysteine was reversing that effect. Unfortunately the drug failed human clinical trials, however, it was shown that individuals who wanted to quit were able to while taking N-acetylcysteine. The drug increases activity of a particular gene that is associated with neuronal plasticity. This finding provides an important link to the findings of Dr. McGehee who discovered that an increase in available receptors led to an increased plasticity in rats. If N-acetylcysteine is involved in regulating plasticity than there could potentially be a correlation. Maybe the gene that N-acetylcysteine acts on has an effect on the number of receptors present on the dopamine neurons. Further investigation into this topic may provide potential benefits to people who suffer from addiction problems. This addiction pathway is generalizable meaning that it can apply to many different types of addictions. Being able to control the plasticity in the dopamine neurons would provide potential therapies to help addicts recover as well as lower their chances of relapse into their old habits. This lower incidence of relapse was also seen in rats after using N-acetylcysteine which is promising for the future in the battle of addiction.

Citations:
Madayag, Aric et al. “Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine.” The Journal of neuroscience : the official journal of the Society for Neuroscience 27.51 (2007): 13968–13976. PMC. Web. 5 Mar. 2016.

Mao, D., K. Gallagher, and D. S. Mcgehee. "Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons." Journal of Neuroscience 31.18 (2011): 6710-720. Web.

University of Cambridge. "Cocaine addiction: Scientists discover 'back door' into the brain." ScienceDaily. ScienceDaily, 12 January 2016. Web.

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https://smartdrugsforcollege.com/n-acetyl-cysteine-benefits/

http://www.alltreatment.com/cocaine-addiction