Alleviation of X-Irradiation-Based Deficit in Memory-Based Learning by D-Amphetamine: Suggestions for Attention Deficit-Hyperactivity Disorder

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 10; pp. 5785 - 5788
• Main Authors: Highfield, D. A., Hu, D., Amsel, A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 12-05-1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Alleys; Amphetamines; Animal models; Animals; Attention Deficit Disorder with Hyperactivity - physiopathology; Attention deficit hyperactivity disorder; Biological Sciences; Brain; Central Nervous System Stimulants - pharmacology; Dams; Dentate gyrus; Dextroamphetamine - pharmacology; Discrimination learning; Discrimination Learning - drug effects; Discrimination Learning - radiation effects; Disease Models, Animal; Experimentation; Hippocampus; Hyperactivity; Hypoplasia; Learning; Memory; Memory, Short-Term - drug effects; Memory, Short-Term - radiation effects; Pups; Rats; Rats, Sprague-Dawley; Rodents; Whole-Body Irradiation; X-rays
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.10.5785

Selective exposure to x-irradiation during infancy, from postnatal days (PND) 2-11 in the rat, results in severe hippocampal granule cell hypoplasia. Preweanling (PND 17-18) rats, which suffer such hippocampal granule-cell agenesis, show deficits in patterned single alternation (PSA), a form of memory-based learning. Deficits in short-term memory along with increased arousal have been suggested as characteristic of children diagnosed with attention deficit-hyperactivity disorder (ADHD). We report here on the ameliorating effects of D-amphetamine, a drug commonly used in the treatment of ADHD, before Ritalin, on PSA, after infantile (PND 2-15) exposure to x-irradiation. After i.p. injections of 0.3 mg/kg D-amphetamine, the onset and magnitude of the PSA memory-based discrimination in the x-irradiated preweanling rats was restored to about the level of controls. These results, showing alleviation of x-irradiation-related deficits in short-term memory by D-amphetamine injections, along with our earlier and present results, showing substantial deficits after x-irradiation alone, encourage the hypothesis that hippocampal granule-cell hypoplasia, which would occur in humans prenatally and is Altman's model of ``minimal brain dysfunction'' [Altman, J. (1986) in Learning Disabilities and Prenatal Risk, ed. Lewis, M. (Univ. of Illinois Press, Urbana), pp. 241-304], may be a factor in at least some forms of ADHD and may provide a basis for an animal model of the disease.