Modulatory Effects of Buspirone on Psychostimulant-Induced Behavioral Alterations under Chronic Restraint Stress in Rats.

Psychostimulants such as methylphenidate (MPH) and modafinil (MOD) are effective in attention-deficit/hyperactivity disorder and narcolepsy but may induce behavioral activation, anxiety-like responses, and cognitive alterations, particularly under stress. Buspirone (BUS), a nonsedative anxiolytic acting as a partial 5-HT1A receptor agonist, may influence stimulant-related behavioral effects. This study evaluated whether BUS modifies behavioral outcomes induced by chronic MPH and MOD administration in rats exposed to repeated restraint stress. Adult male Sprague-Dawley rats received oral MPH (10 mg/kg), MOD (75 mg/kg), BUS (10 mg/kg), or their combinations for 35 days under restrained or nonrestrained conditions. Behavioral assessments included locomotor activity, exploratory performance (open-field and head-dip tests), and memory evaluation using passive avoidance and Morris water maze paradigms. MPH and MOD alone increased locomotor activity and altered exploratory behavior, with effects influenced by stress conditions. BUS coadministration attenuated stimulant-induced hyperactivity and modulated exploratory responses. BUS alone reduced passive avoidance latency, which may reflect anxiolytic effects rather than impaired memory, while combined treatment indicated modulation of stimulant-associated cognitive outcomes. BUS may reduce stimulant-induced behavioral activation under stress, suggesting its potential as an adjunct to improve the behavioral tolerability of psychostimulant therapy.