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In children with attention-deficit/hyperactivity disorder (ADHD), methylphenidate at lower doses is optimal for learning, whereas higher doses improve classroom behavior (Science 1977; 198:1274). Across the age span and in both clinical and healthy populations, methylphenidate can induce agitation and psychosis. To study the pathophysiology of these phenomena, researchers examined behavior and glutamatergic signaling in the prefrontal cortex in adolescent rats injected with low- or high-dose methylphenidate; doses were relevant to those used clinically in humans.
Low doses were associated with improved memory and attention; high doses were associated with worsened memory, inability to complete the attention task, and marked hyperlocomotion. …