anti-Causality


Wednesday, September 26, 2012

Heroin addiction explained in terms of neuro-adaptation (or plasticity)


In the widest sense, neuro-adaptation actually describes the plasticity of the entire neurological system that gives humans (and higher organisms) flexibility.  Permit me to focus on the underlying mechanisms of opioid agonist (heroin or morphine) tolerance and withdrawal as examples using Christie (2008).

In tolerance, adaptive mechanisms start at the target receptor for opioid agonists, MOPr; work within the cells to maintain homeostatic balance (K+ channels and voltage-gated Ca channels); and work at the synapses that connect neurons, upwards to the level of neural networks.  Long-term tolerance can adapt to ten- or hundred-fold increases in effective dose through these processes as the receptors shut down to compensate for the increased agonists.  Sudden cessation -- producing withdrawal syndrome -- impacts the same places in reverse, requiring re-adaptation to readjust to presumably normal levels.

Changes in the homeostatic mechanisms (K+ and Ca+) within cells affect the synapses of the motivational systems, including the reward systems that Jennie mentions.  Initial adaptation (tolerance) can happen quickly (in two phases:  immediate at the cellular level, and gradual throughout the whole system), whereas re-adaptation (withdrawal in these two phases) can take months.  Initial withdrawal peaks as the receptors have no agonists attached to them, causing homeostatic imbalances that users want to restore by filling the receptor with opioid agonists, in other words, a "fix."

Networks adapt in similar (homeostatic) ways but without the influence of opioid agonists, which contributes to long-term addiction issues.  It might be--this is purely speculation on my part--that the stimulus of the opioid agonist sets off a neuroplasticity chain-effect throughout the system, but that the opposite neuroplastic process towards normal restoration has no stimulant, and hence takes longer.

References

Christie, M. J. (2008). Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction. British Journal of Pharmocology 154(2).  Retreived Febuary 25, 2011 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442443/

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