Acute and chronic methylphenidate dose-response assessment on three adolescent male rat strains.
Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to compare whether there were strain differences. An automated, computerized, open-field activity monitoring system was used to study the dose-response characteristics of acute and repeated MPD administration throughout the 11-day experimental protocol. Results showed that all three adolescent rat groups exhibited dose-response characteristics following acute and chronic MPD administration, as well as strain differences. These strain differences depended on the MPD dose and locomotor index. Chronic treatment of MPD in these animals did not elicit behavioral sensitization, a phenomenon described in adult rats that is characterized by the progressive augmentation of the locomotor response to repeated administration of the drug. These results suggest that the animal's age at time of drug treatment and strain/genetic variability play a crucial role in the acute and chronic effect of MPD and in the development of behavioral sensitization.
Yang
Pamela B
PB
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, 740 Westwood Blvd., Room A8-144, Los Angeles, CA 90024, USA.
Swann
Alan C
AC
Dafny
Nachum
N
D000293:Adolescent; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013995:Time
D000697:Central Nervous System Stimulants; D008774:Methylphenidate