Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia.

Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia. Exp Neurol. 2017 Mar 22;: Authors: Meadows SM, Chambers N, Conti MM, Bossert SC, Tasber C, Sheena E, Varney M, Newman-Tancredi A, Bishop C Abstract l-DOPA remains the benchmark treatment for Parkinson's disease (PD) motor symptoms, but chronic use leads to l-DOPA-induced dyskinesia (LID). The serotonin (5-HT) system has been established as a key modulator of LID and 5-HT1A receptors (5-HT1AR) stimulation has been shown to convey anti-dyskinetic effects. However, 5-HT1AR agonists often compromise clinical efficacy or display intrinsic side effects and their site(s) of actions remain debatable. Recently, highly selective G-protein biased 5-HT1AR agonists, F13714 and F15599, were shown to potently target 5-HT1A auto- or hetero-receptors, respectively. The current investigation sought to identify the signaling mechanisms and neuroanatomical substrates by which 5-HT1AR produce behavioral effects. In experiment 1, hemi-parkinsonian, l-DOPA-primed rats received systemic injections of vehicle, F13714 (0.01 or 0.02mg/kg), or F15599 (0.06 or 0.12mg/kg) 5min prior to l-DOPA (6mg/kg), after which LID, motor performance and 5-HT syndrome were rated. Both compounds significantly reduced LID, without affecting motor performance, however, acute administration of F13714 significantly induced 5-HT syndrome at anti-dyskinet...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research