Effects of l-Dopa and pramipexole on plasticity induced by QPS in human motor cortex

Abnormal plasticity has been reported in the brain of patients with Parkinson’s disease (PD), especially in the striatum. Although both l-Dopa and dopamine agonist remain to be the mainstay of the treatment in PD, their differential effects on cortical plasticity are unclear. We applied quadripulse stimulation (QPS) over the primary motor cortex (M1) in ten normal subjects to induce bidirectional long-term motor cortical plasticity. A long-term potentiation (LTP)-like effect was induced in the primary motor cortex (M1) by high-frequency QPS5 (interpulse interval of 5 ms) over M1, whereas a long-term depression (LTD)-like effect was induced by low-frequency QPS50 (interpulse interval of 50 ms), and the effects lasted up to 90 min after the stimulation pulses have ceased. In a double-blind randomized placebo-controlled crossover design, l-Dopa carbidopa 100 mg, pramipexole 1.5 mg [150 mg LED (l-Dopa equivalent dose)], or placebo was administered to the subjects 30 min before applying QPS. l-Dopa enhanced both LTP- and LTD-like plasticity as compared to placebo. In contrast, neither an LTP-like effect nor an LTD-like effect was modulated by pramipexole. The lack of LTP enhancement by pramipexole is compatible with the finding that D1 activation strengthens LTP because pramipexole is almost purely a D2 agonist. The lack of LTD enhancement by pramipexole is also consistent with the finding that both D1 and D2 coactivation is required for LTD. This is the first report to show that dopamine enhances LTD as well as LTP in the human brain and that coactivation of D1 and D2 is a requisite for LTD enhancement in normal humans.