More on neuroplasticity

Neuroplasticity: how our brains re-wire.

Researchers have now shown that long-term changes affect the brain even after drug use has ceased. This concept is especially important in light of the revolutionary idea of neuroplasticity, a conception that has overtaken the field of neuroscience in recent years. The overarching concept of neuroplasticity is that our brains are constantly changing and evolving. Whereas scientists in the field once believed that we were born with all of the brain cells that we would have in our entire life, we now understand that neurons are able to regenerate, and even more importantly, that our brain circuits are able to rewire as a result of experience.  Evidence from research of the past two decades offers support for this theory. Thompson showed that patients suffering from aphasia as a result of brain injury were able to regain linguistic functioning by recruiting new areas of the brain that were not typically central to speech contribution to play a key role in language.[1] Melzack et al. showed that human perception of pain is at least partially the result of past experience that causes the brain to rewire following painful stimuli.[2]

However, evidence in favor of neuroplasticity may seem contradictory in light of the argument that drugs have a long-term effect on the brain. After all, if the brain has the ability to change so much, doesn’t this mean that it will recover from any damage that is caused by drug use? Not necessarily. While the brain is able to recover from some degree of insult, the mechanism that causes drug users to experience a euphoric event is also involved in the long-term changes that result from such abuse. According to Uys and Reissner (Glutamatergic Neuroplasticity in Cocaine Addiction, Progress in Molecular Biology and Translational Science. Vol 98. 2011) despite the fact that initially, drugs such as cocaine activate the dopaminergic pleasure system, long term use of drugs causes the brain to recruit new areas to play a role in the mechanism. The authors state:

Over time and with chronic exposure, other structures involving glutamatergic and GABAergic transmission and the brain stress systems are subsequently recruited in latter stages of addiction. For example, key glutamatergic projections are sent from the [pre-frontal cortex], amygdala, and hippocampus, and GABAergic projections are sent from medium spiny neurons of the [nucleus accumbens] core and shell to the vental pallidum and back to the [ventral tegemental area] (371).  

This statement is central to the concept of addiction. Although the individual may enjoy the first time that he or she uses a given drug and may have a strong desire to use the substance again, the real consequences of addiction usually occur as a result of chronic use. This is at least partially due to the rewiring of the pleasure circuits in the brain. However, arguing that using drugs a single time is safe, given the fact that re-wiring cannot occur on the first exposure, is naïve. Although it may take a number of times to do irreparable remodeling of neurocircuitry, it seems clear that the long term changes that occur are not worth the pleasure that may result. Uys and Reissner offer support for this claim, stating, “Long-term potentiation is observed early in the VTA, following acute exposure to drugs of abuse. This LTP lasts at least 5 days following a single drug exposure” (373).

For more on neuroplasticity, see another post.

Great book on neuroplasticity.

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[1] Thompson, C. K. (2000). Neuroplasticity: Evidence from aphasia. J. Commun. Disord., 33, 357-366.

[2] Melzack, R., Coderre, T. J., Katz, J., & Vaccarino, A.L. (2001). Central neuroplasticity and pathological pain. Annals of the New York Academy of Sciences. 933, 157-174.

Why addicts can't quit their drug, and why "willpower" is not the only factor one should consider.

The short answer: Neuroplasticity.

According to Merriam-Webster online, addiction is the “compulsive need for and use of a habit-forming substance (as heroin, nicotine, or alcohol) characterized by tolerance and by well-defined physiological symptoms upon withdrawal.”

Today my blog entry is going to focus on the physiological mechanisms that underlie addiction, as to explain the changes that occur in the brain as a result of substance abuse. Although some of this information was discussed in my neurobiology class this fall with Dr. Hettes, I am using an article that was given to me by my mentor. It comes from Progress in Molecular Biology and Translational Science (Vol 98): The Brain as a Drug Target. Edited by Rahman, the chapter that I will use is entitled Glutamergic Neuroplasticity in Cocaine Addiction, by Joachim D. Uys and Kathryn J. Reissner.

Although the first time one uses a substance (in this example, we are assuming the substance is cocaine) one does not necessarily become addicted, certain changes do take place in the brain. Generally, dopamine may be released from the ventral tegmental area and may target receptors in different areas including the prefrontal cortex, amygdala, hippocampus, and nucleus accumbens. According to Uys and Reissner, “The projection from the prefrontal cortex to the nucleus accumbens is considered to be a common final pathway engaged in drug-seeking behavior induced by exposure to drug-paired cues, stress, or a drug prime and represents and important site of chronic neuroplastic changes induced by drugs of abuse” (371).

(Used from Dr. Hettes Neurobiology class)

All of this information is important because it deals with the motivational aspect that is involved in the drug seeking behavior that is characteristic of an addict. Long term potentiation is a phenomenon in which, according to Dr. Hettes, “NMDA receptor (a type of ionotropic glutamate receptor) activation results in a calcium ion dependent increase in AMPA receptors (also an ionotropic glutamate receptor) at the synapse.” Because NMDA receptors are dependent on AMPA receptors in order to depolarize the neuronal cell, the placement of more AMPA receptors leads to a greater depolarization of the neuronal cell membrane and thus results in an EPSP (excitatory post-synaptic potential), meaning that it will be easier for a neuron to fire an action potential at this synapse.

(Again, thanks Dr. Hettes).

Okay, maybe that was a little complicated, but I feel like I had to explain that in order to give some background on this next part.

So what does it mean that there is an increase of AMPA receptors in certain areas of the brain (specifically, in the Nucleus accumbens)? An increase in receptors in this area means that the substance abuser is developing a strengthened signal transduction pathway in the area of the brain that is involved in reward, pleasure, and addiction (just to name a few). The motivational aspect to continue the behaviors that result from the cocaine-associated feelings is strengthened.

What are the implications of this?

Even though the addict knows that the actions he or she is undertaking is negative and there might be legal, societal, and moral implications that result from using these drugs, the addicts brain is no longer functioning at the same level as you or I. The drive to use cocaine is increased not only at a psychological level (the feelings that are associated with using drugs) but also at a biological level.

However, one must take into account that separating the aspects of addiction into different areas of science is difficult if not altogether reductionist. The biologic mechanism that induces changes in the brain IS exactly that which is responsible for such drug cravings.

I know my explanation is somewhat simplified, and I hope to go further in depth later on in my postings.