MOTIVATIONAL PROPERTIES OF LEVODOPA IN A BILATERAL 6-OHDA LESION RAT MODEL OF PARKINSON’S DISEASE

Authors: Izabella DiRosa, Christopher Bishop, Julia Maslinksi, Natalia Hakimzadeh

SUNY Campus: Binghamton University

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 50

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

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor dysfunction, largely due to dopamine (DA) neuron loss in the nigrostriatal pathway. DA replacement therapies like L-DOPA, while effective, can lead to complications such as L-DOPA-induced dyskinesia (LID) and DA dysregulation syndrome (DDS), which manifest as abnormal movements and compulsive or impulsive behaviors. Given their impact on quality of life, understanding their mechanisms is paramount. We hypothesized that bilateral 6-OHDA lesions would induce motor deficits, L-DOPA treatment would produce LID, and subjects with the most significant DA loss would exhibit the greatest reinforcing effects. To investigate, 42 male and female Sprague-Dawley rats received bilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the medial forebrain bundle, or no surgical manipulation. Motor impairments were assessed using the forepaw adjusting steps (FAS) and rotarod tests. The conditioned place preference (CPP) paradigm evaluated L-DOPA’s reinforcing properties by measuring preference scores after pairing L-DOPA (12 mg/kg) with a specific environment. LID was assessed using abnormal involuntary movement (AIMs) tests. Results indicate L-DOPA had reinforcing effects in both sham and parkinsonian rats. Ongoing immunohistochemistry (IHC) staining for tyrosine hydroxylase (TH) and FosB is expected to show reduced TH expression and increased FosB activity in DA-lesioned subjects. These findings highlight L-DOPA’s long-term risks and suggest overlapping mechanisms between LID and DDS, informing improved PD treatments.