Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) loss. Patients also experience non-motor symptoms, such as PD-associated psychosis (PDAP). Unfortunately, L-DOPA may increase the risk of developing PDAP. Changes to serotonin (5-HT) and particularly 5-HT 2A receptors (5-HT2ARs) might underlie these risks. We used the hemi-parkinsonian rat model to investigate how DA loss, L-DOPA, and 5-HT2AR activation impacts unconditioned responses (head twitch response (HTR), rearing, and locomotor activity) which are all disrupted in preclinical models of psychosis. In Experiment 1, sham or DA-lesioned rats were treated chronically with L-DOPA or vehicle. After L-DOPA washout rats underwent testing with the 5-HT2AR agonist DOI (0, 0.2, 1.0 mg/kg) and HTR/rearing/locomotion were quantified. Lesioned, L-DOPA treated rats showed a unique reduction in rearing and data suggest unique group-related differences in locomotor activity. These results highlight 5-HT2AR responsivity is modified by DA loss and chronic L-DOPA treatment might that may elevate the risk for 5-HT- linked non-motor neuropsychiatric complications in PD.
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McLune, Annique and D'Almeida, Evan, "The effects of 5-HT2AR stimulation on psychosis-associated behaviors in naive and L-DOPA treated hemiparkinsonian rat" (2020). Research Days Posters Spring 2020. 50.