In a newly published scientific article, researchers show that addictions to cocaine may be the result of the genetic makeup of the brain.; exposure to cocaine in certain individuals may make them more susceptible to developing addictions, and increase their risk of them to relapsing
When tackling addictions, understanding the reasons for why certain individuals are more susceptible to relapse is one of the greatest challenges in addiction treatment. In a recent article published in the Proceedings of the National Academy of Sciences, scientists used rat models to study how the genetic makeup of the brain influences addictions.
In this study, two breeds of rats were used: 1) High-responder rats that respond with rapid movements to novel environments, and are more likely to self-administer drugs, and 2) Low-responder rats that responded with fewer rapid movements in novel environments. Researchers studied their responses and neurological makeup after long-term cocaine exposure. The experiment consisted of two parts: 1) studying the behavioural differences in these two types of rats, and 2) studying the brain for genetic differences that may be influencing behaviour.
In order to study behavioural differences, both rat breeds self-administered cocaine for a prolonged period of time. One behavioural symptom of addiction included continuing to seek out the drug when it was not made available. The tendency for this behaviour to return when rats were presented with certain environmental cues, but no cocaine, was also symptomatic of addiction.
To train the rats to associate environmental stimuli with cocaine, they were exposed to holes where cocaine was administered. When cocaine was made available, a light was turned on. This was repeated for 20 rounds in order to consolidate the association between the light and the cocaine.
When the light was off, high-responder rats were more likely to continue seeking out cocaine relative to their low-responder counterparts after roughly 40 sessions. This indicated that these high-responder rats were more likely to continue seeking out the drug despite the fact that it was no longer available. When the light was turned on but no cocaine was available, high-responder rats had a much higher rate of drug-seeking behaviour than the low-responder rats.
What causes this differential behaviour? To study this, the researchers looked at the brains of rats that had participated in the study (roughly 170 days old), and those that had not participated in the study and died of old age (roughly 70 days old). They found that high-responder rats, both without exposure, and with prolonged exposure to cocaine, had higher levels of a protein in their brain produced by a gene called FGF2 (fibroblast growth factor 2). This gene is a precursor for drug-taking behaviour. In low-responder rats, these genes had higher repressive markers, indicating that a combination of low gene prevalence, and a greater number of repressive markers, may reduce the likelihood of developing a cocaine addiction in these rats.
Additionally, rats with the high-responder behaviours had lower levels of dopamine receptor proteins in the brain, and a higher number of repressive markers for dopamine receptors. Dopamine is a neurotransmitter that is responsible for reward-motivated behaviours, and is typically present in addictive drugs. This reduced availability of receptors in the high-responder rats would indicate that they would feel the need to seek out more of the addictive drug (in this case cocaine) to feel the high that dopamine provides. Interestingly, the difference in dopamine protein levels between the two rat breeds diminishes with prolonged exposure to cocaine. This may be the result of epigenetic changes to the genome in brain cells that results in a lower availability of dopamine receptors in the low-responder behaviour rats. Epigenetics is a way in which environmental influences (such as chemicals) can change the expression of different genes in the body without altering one’s DNA. Instead, it works by changing how DNA is coiled in the cells, and thus which genes are available for protein synthesis.
The researchers believe that it is a combination of this low level of dopamine receptor availability and the high levels of FGF2 proteins that may be a precursor for addictive behaviors seen in the high-responder rats. They believe that this leads them to develop cocaine addictions, and relapse (ie. engage in drug-seeking behaviours) when certain environmental stimuli are present.
So what does this mean for us? The researchers suggest that understanding the factors that influence the susceptibility of some people to cocaine addictions over others will be critical for treatment, and preventing relapse.
Written By: Nicole Pinto, HBSc