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Asked • 03/26/19

Can neurotransmitter depletion cause short-term drug tolerance?

**I'm curious to know if neurotransmitter degradation factors into drug tolerance and neural conduction and, if so, to what extent.** As I recall from textbooks I read as an undergrad, one mechanism of drug tolerance works by increasing the necessary thresh-hold at a synapse such that larger concentrations of neurotransmitter or more-frequent action potentials in the upstream axon were required to depolarize the membrane and propagate the signal. It seems to me that the same effect would occur if there were fewer available molecules of the required neurotransmitter.Does over-stimulation of a neural pathway (through the use of a drug or other stimuli that up-regulates a given neurotransmitter) shorten the half-life of the neurotransmitters it uses? Could a diet which is poor for necessary precursor nutrients cause a person's neurotransmitter concentrations to drop and reduce signaling along specific neural pathways? Could lack of sleep or other physiological stressors have a similar effect? I am not a neuroscientist so please correct (and forgive) me if I'm using any terms incorrectly or am flat-out wrong in any of my assumptions.

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