ArticlePsychopharmacology2026
Novel dopamine 4 receptor ligands differentially ameliorate ADHD-like behaviors in spontaneously hypertensive rats.
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
rationaleDopamine D4 receptors (D4Rs) have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), yet their precise role and therapeutic relevance remain underexplored. Highly selective D4R compounds may provide a valuable tool to elucidate D4R function and assess their potential as non-stimulant ADHD treatments.
objectivesThis study examined the behavioral effects of two novel D4R drugs, namely, FMJ-01-38 (high-efficacy partial agonist) and FMJ-01-54 (full antagonist) in adolescent spontaneously hypertensive rats (SHR/NCrl), a validated ADHD animal model, and Wistar (control) rats.
methodsRats received intraperitoneal injections of FMJ-01-38 or FMJ-01-54 (5-10 mg/kg), or vehicle prior to behavioral assays assessing locomotor activity (open field tests), recognition memory (novel object preference test), spatial working memory (Y-maze test), and impulsivity (delay discounting task).
resultsFMJ-01-38 dose-dependently reduced locomotor hyperactivity and improved spontaneous alternation in SHR/NCrl; at 5 mg/kg, it also enhanced novel object preference and reduced impulsive choice and action, indicating attenuation of ADHD-like behaviors and improved cognitive function. FMJ-01-54 produced similar improvements in Y-maze and novel-object performance without altering locomotor activity or impulsivity of SHR/NCrl, suggesting selective cognitive improvement. In Wistar rats, FMJ-01-38 increased novel object preference only at the 5 mg/kg dose, while FMJ-01-54 treatment did not produce any significant behavioral effects.
conclusionsThese findings demonstrate that D4R modulation, through either partial agonism or antagonism, differentially ameliorates ADHD-related behaviors and improves cognitive performance. Both FMJ-01-38 and FMJ-01-54 produced minimal effects in control animals, suggesting pathology-specific efficacy and highlighting D4R ligands as promising non-stimulant therapeutic candidates for ADHD.
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