ArticlePsychopharmacology2026
Dexmedetomidine attenuates methamphetamine-induced hyperthermia and hyperlocomotion in male rats and modulates monoamine dynamics in the anterior hypothalamus.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
rationaleMethamphetamine (METH) intoxication is associated with serious complications, including hyperthermia and agitation, which are major contributors to morbidity and mortality. Currently, no established pharmacological interventions are available for these conditions.
objectivesTo evaluate the effects of dexmedetomidine (DEX)-an α2-adrenergic receptor agonist-on METH-induced hyperthermia and hyperlocomotion, and explore the underlying mechanisms, with a particular focus on central monoamine dynamics.
methodsMale Wistar rats were administered METH (5 mg/kg, intraperitoneally) following pretreatment with DEX (0.1 or 0.5 mg/kg), guanfacine (α2A agonist), NBP (α2C agonist), or vehicle. Body temperature and locomotor activity were continuously monitored using an implantable telemetry device. In vivo microdialysis in the anterior hypothalamus (AH) was conducted to measure extracellular concentrations of dopamine (DA), noradrenaline (NA), and serotonin (5-HT).
resultsDEX dose-dependently attenuated METH-induced hyperthermia and hyperlocomotion. Guanfacine produced comparable suppressive effects, whereas NBP showed no significant efficacy, suggesting predominant involvement of α2A receptors. METH markedly increased extracellular DA, NA, and 5-HT levels in the AH, with NA exhibiting the greatest increase. DEX notably suppressed elevations in DA and NA without significantly impacting 5-HT levels.
conclusionsDEX attenuated METH-induced hyperthermia and behavioral activation, likely via α2A-adrenergic mechanisms. DEX also suppressed METH-induced central monoamine release, particularly NA and DA release, in the anterior hypothalamus. Thus, DEX is a potential therapeutic candidate for managing the severe complications associated with METH intoxication.
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