Theophylline impairs memory/learning in developing mice.
We studied the relationship between theophylline and memory/learning using an elevated plus-maze test and measuring spontaneous locomotor activity in developing mice. There were no significant differences in transfer latency (TL) in 21-, 30- and 42-day-old mice in the acquisition trial, but theophylline significantly prolonged TL in comparison with the control group in 21- and 30-day-old mice in the retention trial (n = 20; 21-day-old mice, P = 0.0009; 30-day-old mice, P = 0.03). The dose-dependent stimulant effects of theophylline were shown in spontaneous locomotor activity (n = 16; 21-day-old mice, P = 0.0005; 30-day-old mice, P = 0.0007; 42-day-old mice, P = 0.0003) in all groups and in rearing in 21-day-old mice (P = 0.02) 1 h after drug administration, but there were no significant effects 24 h after drug administration in all groups. Our study showed that even a therapeutic dose of theophylline impaired memory/learning only in developing mice, and theophylline increased locomotor activity both in developing and adolescent mice. These observations are consistent with several clinical studies, which reported the relationships between theophylline use and memory/learning and learning-related behaviors in children, such as difficulty in studying and hyperactivity. Theophylline possibly induces memory/learning disabilities and hyperactivity in infants and young children.
Hirose
Mieko
M
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai city 980-8574, Japan. mhirose@ped.med.tohoku.ac.jp
Yokoyama
Hiroyuki
H
Iinuma
Kazuie
K
D000367:Age Factors; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology; D007859:Learning Disabilities / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000009:adverse effects*
D001993:Bronchodilator Agents; D013806:Theophylline