Psychostimulants and metaplasticity

While all medicaments are checked for toxic and other harmful effects, their possible influence on plasticity in the CNS often are simply unknown. Several psychostimulants such as methylphenidate (MPH; “Ritalin”) or 3,4-Methylenedioxymethamphetamine (“Ecstasy”) modulate synaptic plasticity in rodents in the hippocampus and the prefrontal cortex. We could demonstrate that these changes are due to polysynaptic mechanisms involving noradrenaline, dopamine and serotonin receptors bringing an increased number of glutamate AMPA receptors to the postsynaptic surface. Further, doses of that improve visuo-spatial learning enhance long-term potentiation. Surprisingly, changes in synaptic efficacy could be seen up to five months after repetitive administration of clinically relevant doses. If we extrapolate these data from rodents to humans, we would face an effect that may last for several years. Thus, we think that metaplastic effects should be more investigated and considered in the long-term use of psychostimulants in therapy or in other contexts.

This study was supported by FONDECYT, Nr. 1120580, Chile