ArticleFrontiers in neural circuits2024
The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.
Article in Frontiers in neural circuits, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Predictive validation of the repeated low-dose reserpine rodent model of parkinsonism.Experimental brain research · 2026Article
- Involvement of Neuroinflammation and Oxidative Stress in L-DOPA-Induced Dyskinesia in Parkinson's Disease: Role of Renin-Angiotensin System and ROCK Pathway.Antioxidants (Basel, Switzerland) · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Introduction: Parkinson's disease (PD) is commonly characterized by severe dopamine (DA) depletion within the substantia nigra (SN) leading to a myriad of motor and non-motor symptoms. One underappreciated and prevalent non-motor symptom, Parkinson's disease-associated psychosis (PDAP), significantly erodes patient and caregiver quality of life yet remains vastly understudied. While the gold standard pharmacotherapy for motor symptoms Levodopa (LD) is initially highly effective, it can lead to motor fluctuations like LD-induced dyskinesia (LID) and non-motor fluctuations such as intermittent PDAP. One source of these fluctuations could be the serotonergic raphe nuclei and their projections. Serotonin (5-HT) neurons possess the machinery necessary to convert and release DA from exogenous LD. In DA-depleted brain regions these 5-HT projections can act as surrogates to the DA system initially compensating but chronically leading to aberrant neuroplasticity which has been linked to LID and may also contribute to non-motor fluctuations. In support, recent work from our lab established a positive relationship between LID and PDAP in parkinsonian rats. Therefore, it was hypothesized that normalizing 5-HT forebrain input would reduce the co-expression of LID and PDAP. Methods: To do so, we expressed 5-HT projection specific inhibitory designer receptor exclusively activated by designer drugs (DREADDs) using Cre-dependent AAV9-hM4di in tryptophan hydroxylase 2 (TPH2)-Cre bilaterally 6-OHDA-lesioned rats. Thereafter we used the designer drug Compound 21 to selectively inhibit 5-HT raphe projections during LD treatment to modulate the expression of PDAP, assayed by prepulse inhibition (PPI) and LID, quantified by the abnormal involuntary movements (AIMs) test. Results: Our results suggest that chemogenetic inhibition of 5-HT raphe-projecting cells significantly reduces LID without affecting stepping ability or established sensorimotor gating deficits. Discussion: Overall, this study provides further evidence for the complex influence of 5-HT raphe-projecting neurons on LD's neurobehavioral effects.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.