Common Pathways of Addiction

A growing amount of research has been centered on finding a common pathway in all drugs of abuse. Common models include reward system pathways and pathophysiological models of pathways including macro- and micro- level structural changes. As stated in lecture, these pathways are “second messengers” acting on chemical interactions and causing some kind of alteration on the neuronal or chemical level (Donaldson, 2017). Additionally a common theme seen in all pathophysiological and behavioral models of addiction is the enactment of endogenous receptors. For example as Lasley (2009) points out alcohol releases endogenous opioids in synapse causing euphoria.

The primary focus of this paper is to summarize and expound upon the accumulated knowledge and research trends on common pathways as presented by Le Moal and Koob (2007) with primary emphasis on neuroadaptional perspectives. Applying opponent process theory to pathophysiological addiction, Le Moal and Koob (2007) describe a pathway that begins as a rush or “affective process” which acts as an unconditional reaction. Depending on the behavioral and neurological underpinnings of the individual as well as contextual components, the drug can range in magnitude of reaction. A b-process is initiated which is sensitization. According to their research noncompetitive glutamate receptor antagonist MK-801 can prevent opioid related hyperalgesia (Le Moal and Koob, 2007). When taken in summation with the idea posited by Nestler (2005) that “methadone, buprenorphine, and naltrexone, which are, respectively, an agonist, partial agonist and antagonist” a common pathway is demonstrated. It is demonstrated by showing that each of these impulsive uses can be blocked from becoming compulsive with intervention at the receptor level. Acamprosate, as another example, has a potential mechanism by which NMDA glutamatergic receptor function is reduced helping to reduce the effects of alcohol addiction (Nestler, 2005). The relevance of these points to Le Moal and Koob’s pathway model is that with competition at the receptor site, the reinforcing nature of the b-process compulsion seeking is reduced.

The idea of opponent process from a more physiological perspective is described by a process Le Moal and Koob (2007) as going through allostasis and neuroadaptation. In this model there is activation of the hippocampus-pituitary-adrenal axis correlated to the failure to regulate impulse control. Additionally there are decreases in the function of neurotransmitters (Le Moal and Koob, 2007). These two parts account for the impulsivity of use and connect to the transition to compulsivity via the sensitization process. Once a drug addiction is at the compulsive level it is acting on corticotropin-releasing-hormone systems as the addicted brain stresses about and is consumed with the idea of getting high (Le Moal and Koob, 2007).

These findings make sense in light of work by Li et al (2008) who offered 18 novel pathways through which addiction could be acting. Upstream (macrolevel) changes include increases in insulin and calcium signaling that present similarly to long-term potentiation. This coincides with the notion that as an addiction becomes compulsive, the anxiety and intrusiveness of thought will rewire and learn to associate relief of anxiety with obtainment of drug. This interplays nicely with what Le Moal and Koob (2007) discuss as neuroplasticity being mediated by the ventral-striatal-pallidal-thalamic cortical system which interacts with a faulty reward system as regulated by the amygdala. These changes in reward circuitry and pathophysiological changes of macro- and micro- (dendrite changes & etc.) are an important pathway to consider when discussing addiction. They open the possibility for treatments as well as an understanding of how anxiety and mood disorders act as the mediator for the transition from impulsive to compulsive reward seeking behavior.

 

REFERENCES

Koob, G.F., & Le Moal, M. (2007). Drug addiction: Pathways to the disease and pathophysiological perspectives. European neuropsychopharmacology, 7(6-7), 377-393.

Li, C.Y., Mao, X., & Wei, L. (2008). Genes and common pathways underlying drug addiction. Plos computational Biology, 4(1), 28-34.

 

Nestler, E.J. (2005). Is there a common molecular pathway for addiction? Nature Neuroscience, 8(11), 1445-1449.

Lasley, E.N. (2009). Progress report 2009: Substance abuse the 2009 progress report on brain research. The Dana Foundation. New York, NY.

Donaldson, T. (2017). Class lecture. UMass Boston.

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