Anti-dyskinetic effects of novel serotonergic combination drug therapy in a hemiparkinsonian rat model of levodopa-induced dyskinesia

Authors: Emma Sarinick, Christopher Bishop, Jacob Jodlowski, Balqiisa J-Elmi

SUNY Campus: Binghamton University

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 17

Timeslot: Session A 9:00-10:00 AM

Abstract: Parkinson’s Disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of nigrostriatal dopamine (DA) neurons producing symptoms of rigidity, tremors, and bradykinesia. While Levodopa (L-DOPA) is the gold-standard therapy, long term use can lead to adverse effects including abnormal involuntary movements (AIMS) known as L-DOPA induced dyskinesia (LID). Previous studies show serotonin (5-HT) 1A receptor (5-HT1AR) agonist Vortioxetine (VTX) and 5-hydroxytryptophan (5-HTP) alleviate LID when individually paired with L-DOPA. In this study, male and female Sprague-Dawley rats (N = 53) received coadministration of VTX and 5-HTP to explore a synergistic effect on LID while retaining motor efficacy. Subjects were rendered hemiparkinsonian through a unilateral 6-hydroxydopamine lesion into the medial forebrain bundle. Following recovery, lesioned rats, determined by forepaw adjusting steps (FAS) test, were rendered dyskinetic assessed via AIMs testing throughout a 2 week period of daily L-DOPA (6 mg/kg, s.c) treatment. In Experiment 1, VTX (1 mg/kg, s.c.) and 5-HTP (10 mg/kg, i.p.) were counterbalanced and acutely injected in a within-subjects design. For Experiment 2, VTX (1 mg/kg, s.c.) and 5-HTP (10 mg/kg, i.p.) were administered daily for 2 weeks in a between-subjects design. For both experiments, AIMs and FAS were implemented to assess alterations in LID and motor efficacy, respectively. Preliminary results revealed coadministration of VTX and 5-HTP with L-DOPA attenuated dyskinesia while maintaining the motor benefits of L-DOPA, thus supporting it as a translational therapy for PD patients to improve long term treatment.