Journal article
The Long-Acting D3 Partial Agonist MC-25-41 Attenuates Motivation for Cocaine in Sprague-Dawley Rats
Biomolecules (Basel, Switzerland), v 10(7), pp 1-16
18 Jul 2020
PMID: 32708461
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The dopamine D3 receptor is a prime target for developing treatments for cocaine use disorders (CUDs). In this study, we conducted a pre-clinical investigation of the therapeutic potential of a long-acting, D3 receptor partial agonist, MC-25-41. Male rats were pre-treated with MC-25-41 (vehicle, 1.0, 3.0, 5.6, or 10 mg/kg, intraperitoneal (IP)) five minutes prior to tests of cocaine or sucrose intake on either a progressive ratio schedule of reinforcement or a variable interval 60 s multiple schedule consisting of 4, 15-min components with sucrose or cocaine available in alternating components. A separate cohort of rats was tested on a within-session, dose-reduction procedure to determine the effects of MC-25-41 on demand for cocaine using a behavioral economics analysis. Finally, rats were tested for effects of MC-25-41 on spontaneous and cocaine-induced locomotion. MC-25-41 failed to alter locomotion, but reduced reinforcement rates for both cocaine and sucrose on the low-effort, multiple schedule. However, on the higher-effort, progressive ratio schedule of cocaine reinforcement, MC-25-41 reduced infusions, and active lever presses at doses that did not alter sucrose intake. The behavioral economics analysis showed that MC-25-41 also increased cocaine demand elasticity compared to vehicle, indicating a reduction in consumption as price increases. Together, these results suggest that similar to other D3-selective antagonists and partial agonists, MC-25-41 reduces motivation for cocaine under conditions of high cost but has the added advantage of a long half-life (>10 h). These findings suggest that MC-25-41 may be a suitable pre-clinical lead compound for development of medications to treat CUDs.
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Details
- Title
- The Long-Acting D3 Partial Agonist MC-25-41 Attenuates Motivation for Cocaine in Sprague-Dawley Rats
- Creators
- Gregory L. Powell - Arizona State UniversityMark D. Namba - Arizona State UniversityAnnika Vannan - Arizona State UniversityJohn Paul Bonadonna - Arizona State UniversityAndrew Carlson - Arizona State UniversityRachel Mendoza - Arizona State UniversityPeng-Jen Chen - Temple UniversityRobert R. Luetdke - University of North TexasBenjamin E. Blass - Temple UniversityJanet L. Neisewander - Arizona State University
- Publication Details
- Biomolecules (Basel, Switzerland), v 10(7), pp 1-16
- Publisher
- Mdpi
- Number of pages
- 16
- Grant note
- DA023957 / National Institute on Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000557168800001
- Scopus ID
- 2-s2.0-85088163044
- Other Identifier
- 991021955154304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology