The activations of calcium/calmodulin-dependent protein kinase II in hippocampus and nucleus accumbens of rats after methylphenidate injection.
Attention-deficit hyperactivity disorder (ADHD) is characterized by a history of impulsivity, hyperkinesis, short attention span, and poor peer relations. Treatment of ADHD with stimulants, such as methylphenidate, reduces motor activity and improves performance of tasks requiring attention, learning, and memory. The ADHD children may have a central neurophysiological disturbance involving catecholamine metabolism. However, the ADHD children may have deviation in the reticular system, which causes them difficulty in sensory integration and eventually disturbs their attention span. In addition, a recent study reports that methylphenidate enhances motivational strength of the ADHD children. Therefore, ADHD pathology may not be as simple as just an "uninhibitory" locomotor activity; several systems must have been affected. The present research aimed to clarify each specific component of behavior, and to trace the possible neural substrate involved. Male Wistar rats of three different ages were used to distinguish the biological maturation effect on the locomotor activity. The methylphenidate-injected rats showed significantly higher activity times (AT) compared to the controls at 8 and 12 weeks old. The in-vitro kinase assay results show that CaM-kinase II in the hippocampus and nucleus accumbens of methylphenidate-injected rats had significantly higher calcium independent activity compared to the controls at 12 weeks old. Furthermore, the percentage of calcium independent CaM-kinase II activity in the nucleus accumbens was directly correlated with AT. This suggests that the underlying mechanism of the effect of methylphenidate might be via CaM-kinase II activation in nucleus accumbens.
Tan
S E
SE
Department of Psychology, Kaohsiung Medical University, Taiwan, Republic of China.
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases