ArticleThe international journal of neuropsychopharmacology2019
Tropisetron Facilitates Footshock Suppression of Compulsive Cocaine Seeking.
Article in The international journal of neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- The recreational-to-habitual shift in psychostimulant use is an economic demand parameter that is unrelated to drug consumption levels (under normal and punishment conditions).bioRxiv : the preprint server for biology · 2026Article
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- Random interval schedule of reinforcement influences punishment resistance for cocaine in rats.Neurobiology of learning and memory · 2024Article
- Punishment resistance for cocaine is associated with inflexible habits in rats.Addiction neuroscience · 2024Article
- Article
- Evaluation of the 5-HTPharmacological reports : PR · 2023Article
- Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.Addiction neuroscience · 2022Article
- Animal Models of the Behavioral Symptoms of Substance Use Disorders.Cold Spring Harbor perspectives in medicine · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing.
methodsRats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task.
resultsThe rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration.
conclusionsThese results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.
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