Department of Neurology, The University of Arizona, Tucson, AZ 85724, USA; Department of Surgery, The University of Arizona, Tucson, AZ 85724, USA; Department of Neurosurgery, The University of Arizona, Tucson, AZ 85724, USA. Electronic address: mbartlet@arizona.edu.
2 papers in the library · 17 citations · publishing 2024-2025
Sub-anesthetic ketamine reduces levodopa-induced dyskinesia (LID) in a rat model of Parkinson's disease, and this anti-dyskinetic effect persists even when opioid receptors are blocked by naloxone at 3 or 5 mg/kg. The higher naloxone dose extended the time course of LID, suggesting opioid receptor activation plays a modulatory role but is not required for ketamine's anti-dyskinetic action. In contrast, naloxone enhanced ketamine's anti-parkinsonian effect, further reducing akinesia. These findings indicate that opioid receptor blockade differentially affects ketamine's anti-parkinsonian and anti-dyskinetic properties, offering mechanistic insight for repurposing ketamine to treat LID in Parkinson's disease.
In a rat model of Parkinson's disease and levodopa-induced dyskinesia (LID), correlations between movement, gamma-band activity, and single-unit firing in primary motor cortex were high under control conditions but decreased considerably after levodopa administration, suggesting the motor cortex becomes functionally decoupled from ongoing movements during LID. This decoupling occurred in both dopamine-depleted and non-depleted hemispheres. Ketamine (20 mg/kg) disrupted finely tuned gamma oscillations, reduced LID, and moderately increased single-unit correlations with movement, but did not enhance gamma-band correlations with movement. Ketamine also reorganized cell-pair firing-rate correlations, inducing a distinct neural ensemble state in LID animals. The findings suggest the motor cortex does not directly trigger specific dyskinetic movements but may permit aberrant movements to emerge in downstream circuits.