1. Risperidone suppresses caffeine-induced hyperthermia and hyperactivity in rats.
- Author
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Takano M, Okada T, Shioda K, Yonekawa C, and Suda S
- Subjects
- Animals, Male, Rats, Sprague-Dawley, Dopamine metabolism, Rats, Hyperkinesis chemically induced, Hyperkinesis prevention & control, Central Nervous System Stimulants pharmacology, Central Nervous System Stimulants toxicity, Norepinephrine metabolism, Caffeine pharmacology, Risperidone pharmacology, Hyperthermia chemically induced, Serotonin metabolism
- Abstract
Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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