Title: The macrocyclic lactones ivermectin and moxidectin show differential effects on rotational behavior in the 6-hydroxydopamine mouse model of Parkinson's disease - PubMed URL Source: https://pubmed.ncbi.nlm.nih.gov/32668263/ Markdown Content: Actions . 2020 Sep 1:393:112804. doi: 10.1016/j.bbr.2020.112804. Epub 2020 Jul 12. Affiliations * PMID: **32668263** * DOI: [10.1016/j.bbr.2020.112804](https://doi.org/10.1016/j.bbr.2020.112804) ## The macrocyclic lactones ivermectin and moxidectin show differential effects on rotational behavior in the 6-hydroxydopamine mouse model of Parkinson's disease Alicia M P Warnecke et al. Behav Brain Res.2020. ## Abstract Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and cognitive deficits, the result of dopamine (DA)-depletion within the basal ganglia. Currently, DA replacement therapy in the form of Sinemet (L-DOPA plus Carbidopa) provides symptomatic motor benefits and remains the "gold standard" for treatment. Several pharmacological approaches can enhance DA neurotransmission including the administration of DA receptor agonists, the inhibition of DA metabolism, and enhancing pre-synaptic DA release. DA neurotransmission is regulated by several receptor subtypes including signaling through the purinergic system. P2 × 4 receptors (P2 × 4Rs) are a class of cation-permeable ligand-gated ion channels activated by the synaptic release of extracellular adenosine 5'-triphosphate (ATP). P2 × 4Rs are expressed throughout the central nervous system including the dopaminergic circuitry of the substantia nigra, basal ganglia, and related reward networks. Previous studies have demonstrated that P2 × 4Rs can modulate several DA-dependent characteristics including motor, cognitive, and reward behaviors. Ivermectin (IVM) and moxidectin (MOX) are two macrocyclic lactones that can potentiate P2 × 4Rs. In this study, we sought to investigate the role of P2 × 4Rs in mediating DA neurotransmission by exploring their impact on DA-dependent behavior, specifically rotation frequency in the unilateral 6-hydroxydopamine-lesioned mouse model of DA-depletion. While we did not observe any differences in the degree of lesioning based on immunostaining for tyrosine hydroxylase between sexes, male mice displayed a greater number of rotations with L-DOPA compared to female mice. In contrast, we observed that IVM plus L-DOPA increased the number of rotations (per 10 min) in female, but not male mice. These findings highlight the potential role of pharmacologically targeting the purinergic receptor system in modulating DA neurotransmission as well as the importance of sex differences impacting outcome measures. **Keywords:** ATP; Adenosine; Dopamine; Motor behavior; P2X4 receptors; Purine. Copyright © 2020 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of Competing Interest There are no declarations of interests to declare. ## Similar articles * [Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: motor impairments identify extent of dopamine depletion at three different lesion sites.](https://pubmed.ncbi.nlm.nih.gov/22146593/) Heuer A, Smith GA, Lelos MJ, Lane EL, Dunnett SB.Heuer A, et al.Behav Brain Res. 2012 Mar 1;228(1):30-43. doi: 10.1016/j.bbr.2011.11.027. Epub 2011 Nov 28.Behav Brain Res. 2012.PMID: 22146593 * [The 6-OHDA mouse model of Parkinson's disease - Terminal striatal lesions provide a superior measure of neuronal loss and replacement than median forebrain bundle lesions.](https://pubmed.ncbi.nlm.nih.gov/25841616/) Bagga V, Dunnett SB, Fricker RA.Bagga V, et al.Behav Brain Res. 2015 Jul 15;288:107-17. doi: 10.1016/j.bbr.2015.03.058. 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Epub 2019 May 4.Neurochem Res. 2019.PMID: 31054067 Free PMC article.Review. ## Cited by * [Ivermectin increases striatal cholinergic activity to facilitate dopamine terminal function.](https://pubmed.ncbi.nlm.nih.gov/38632622/) Wadsworth HA, Warnecke AMP, Barlow JC, Robinson JK, Steimle E, Ronström JW, Williams PE, Galbraith CJ, Baldridge J, Jakowec MW, Davies DL, Yorgason JT.Wadsworth HA, et al.Cell Biosci. 2024 Apr 17;14(1):50. doi: 10.1186/s13578-024-01228-2.Cell Biosci. 2024.PMID: 38632622 Free PMC article. ## Publication types * Actions * Actions * Actions ## MeSH terms * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions * Actions ## Substances * Actions * Actions * Actions * Actions * Actions * Actions ## LinkOut - more resources * ### Full Text Sources * [Elsevier Science](https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(20)30503-9) * [Ovid Technologies, Inc.](https://www.ovid.com/32668263.pmid) * ### Medical * [MedlinePlus Health Information](https://medlineplus.gov/parkinsonsdisease.html)