Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson’s disease

Abstract

<jats:title>Abstract</jats:title><jats:p>Parkinson’s disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID.</jats:p>

Pallidal Structural Changes Related to Levodopa-induced Dyskinesia in Parkinson's Disease

“…Additionally, various hypotheses, including pre-synaptic and post-synaptic changes in the basal ganglia, are suggested for LID in PD (Iravani and Jenner, 2011;Phillips et al, 2016), but the main mechanism underlying LID is pulsatile stimulation of the striatal postsynaptic receptors. In patients with PD, dopaminergic modulation of the striatal activity and compensatory mechanism are already impaired; therefore, exogenous administration of repeated doses of levodopa induces molecular and neurophysiological changes (Calabresi et al, 1993), and abnormal firing pattern of the basal ganglia neuron (DeLong, 1990).…”