Differential effects of opioid receptor antagonism on the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine treatment in a preclinical model.
Neuropharmacology October 1, 2024 Carolyn J Stopera, Mitchell J Bartlett, Chenxi Liu et al. 9 citations
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.