Influence of 5-HT Circuitry on Visual Prepulse-inhibition in a Unilateral Parkinsonian Rat Model

Authors: Haley Prisinzano, Christopher Bishop, Shruti Venkatesh, Natalie Lipari

SUNY Campus: Binghamton University

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 46

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

Abstract: Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by dopamine (DA) depletion in the substantia nigra pars compacta (SNc), leading to motor and non-motor symptoms, including Parkinson’s Disease-associated psychosis (PDAP). Visual hallucinations are common in PDAP and significantly impair quality of life. While the mechanisms are unclear, serotonin 5-HT2A receptors are likely involved. This study investigates 5-HT circuitry using visual prepulse inhibition (PPI) in a hemiparkinsonian rat model. Sprague-Dawley rats received unilateral 6-hydroxydopamine (6-OHDA) or vehicle injections to induce a hemiparkinsonian state, followed by the forepaw adjusting steps (FAS) test to confirm lesion efficacy. Both groups underwent 30 minutes of PPI testing to assess DA loss effects. In a second experiment, additional sham and lesion animals underwent 3 days of PPI after receiving different doses of the 5-HT2A receptor agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). Both experiments included a 90-minute head twitch response (HTR) and rearing test to measure hallucinogenic behaviors and 5-HT2A activation. Brain tissue was collected for high-performance liquid chromatography (HPLC) analysis. Experiment 1 showed no significant lesion-induced deficit in visual PPI. In Experiment 2, 0.25 mg/kg DOI altered overall startle amplitude between sham and lesion groups, while 1 mg/kg significantly increased head twitches in all animals. HTR findings were comparable to the literature, but PPI results suggest further research is needed to clarify 5-HT’s role in PDAP.