Inhibitory Effect of Apomorphine on Focal and Nonfocal Plasticity in the Human Motor Cortex

Area of Science:

• Neuroscience
• Neuropharmacology
• Motor Control

Background:

• Dopamine is vital for neuroplasticity, underpinning learning and memory.
• Dopamine's effect on plasticity (LTP/LTD) depends on receptor subtype, concentration, and induction method.
• Levodopa (L-DOPA) shows dose-dependent effects on motor cortex plasticity, with medium doses preserving it.

Purpose of the Study:

• To investigate the dosage-dependent effects of the nonselective dopamine agonist apomorphine on human motor cortex plasticity.
• To compare apomorphine's effects to previously observed L-DOPA effects.
• To explore apomorphine's impact on both focal and nonfocal plasticity induction.

Main Methods:

• Healthy participants received 0.1, 0.2, or 0.3 mg apomorphine, or placebo.
• Nonfocal plasticity was induced using paired associative stimulation (PAS).
• Focal plasticity was induced using transcranial direct current stimulation (tDCS).
• Motor cortical excitability was monitored using transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs).

Main Results:

• Apomorphine demonstrated an inhibitory effect on both focal and nonfocal LTP-like and LTD-like plasticity across all tested dosages.
• Plasticity was abolished, diminished, or reversed under apomorphine treatment.
• These detrimental effects suggest a predominantly presynaptic mechanism of action for the studied apomorphine dosages.

Conclusions:

• Unlike L-DOPA's complex dose-response, apomorphine exhibited a uniformly inhibitory effect on motor cortex plasticity in healthy subjects.
• The findings highlight the critical role of dopamine receptor modulation in regulating neuroplasticity.
• The results suggest apomorphine, at these doses, may negatively impact learning and memory processes dependent on motor cortex plasticity.