Srpski arhiv za celokupno lekarstvo 2012 Volume 140, Issue 1-2, Pages: 14-21
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Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study
Ilić Nela V., Petronić Ivana, Grajić Mirko, Ilić Tihomir V.
Introduction. Administration of pharmacological agents with specific actions
on neurotransmitter systems is a powerful driver of functional cortical
reorganization. Plastic reorganization of the motor cortex in humans studies
by the use of non-invasive stimulation protocols, which mimic the Hebbian
model of associative plasticity. Objective. Aiming to explore pharmacological
modulation on human motor cortex plasticity, we tested healthy subjects after
each dosage of diazepam, levodopa i placebo administration, using paired
associative stimulation protocol (PAS) that induce fenomena similar to a
long-term potentiation and depression, as defined on the synaptic level.
Methods. We analyzed effects of benzodiazepines (10 mg), levodopa (200 mg)
and placebo on PAS protocol in 14 healthy volunteers, using a double-blind
placebo-controlled study design. PAS consisted of electrical stimuli pairs at
n.medianus and magnetic pulses over the scalp (transcranial magnetic
stimulation) in precisely defined intervals (ISI was 10 and 25 ms) for a
total of about 15 minutes (200 pairs). MEP amplitudes before and after (0,
10, 20 and 30 minutes later) interventional protocols were compared. Results.
When protocols were applied with placebo depending on ISI (10 ms -
inhibitory, 25 ms - facilitatory effects), MEP amplitudes decreased or
increased, while values in the postinterventional period (0, 10, 20 and 30
min) were compared with initial values before the use of SAS. The use of
benzodiazepines caused the occlusion of LTP-like effect, in contrast to
amplification effects recorded after the administration of levodopa. With
respect to the LTD-like protocol, the reverse was true (ANOVA for repeat
measurements p<0.001). Conclusion. Administration of GABA-ergic agonist
diazepam interferes with the induction of associative plasticity in the motor
cortex of healthy individuals, as opposed to the use of levodopa, which
stimulates these processes. The observed effects point at a potential role of
pharmacological modulation of plasticity in humans.
Keywords: transcranial magnetic stimulation, paired associative stimulation, motor cortex, cortical plasticity