The Effects of Selective Blockade of the Serotonin Transporter on Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease

Authors: Ethan Valle, Christopher Bishop, Jiaer Huang

SUNY Campus: Binghamton University

Presentation Type: Poster

Location: UU 108

Presentation #: 81

Timeslot: Session D 3:00-4:00 PM

Abstract: Parkinson’s Disease (PD) is a neurodegenerative hypokinetic motor disorder resulting from the loss of dopamine (DA) neurons in the substantia nigra (SN). In early disease stages, DA replacement with the drug L-3,4-dihydroxyphenylalanine (L-DOPA) effectively restores motor function, however, within 10 years of chronic treatment, up to 90% of PD patients will develop abnormal involuntary movements (AIMs) called L-DOPA-induced dyskinesia (LID). The pathogenic mechanisms of LID are complex, but accumulating evidence has implicated aberrant neuroplasticity within dorsal raphe (DR)-striatal serotonin (5-HT) circuits and the 5-HT transporter (SERT) has been targeted for antidyskinetic adjuncts. This study investigates the effects of SERT-blocker citalopram administered via intra-raphe, intra-striatal, or systemically on LID and motor performance. Male and female Sprague Dawley rats were rendered hemiparkinsonian with unilateral 6-hydroxydopamine (6-OHDA) lesions. A subset of rats were implanted with cannulae situated above the DR nucleus or the striatum ipsilateral to the lesion. All animals were treated daily with L-DOPA (12 mg/kg; s.c.) to establish LID before undergoing counterbalanced coadministration testing with citalopram (10 µg; i.c.v. or 5 mg/kg; s.c.). Animals were evaluated for AIMs and motor efficacy. Preliminary results suggest that citalopram reduces LID by blocking SERT in the DR while also maintaining L-DOPA’s motor enhancement, thus providing a potential treatment modality for patients.