Repeated treatment with methylphenidate (MPD; Ritalin) and other psychomotor stimulants, such as amphetamine and cocaine, has been shown to cause behavioral sensitization in rats and humans. Behavioral sensitization is characterized by an increase in locomotor and/or stereotypic behavior. It is not known, however, whether the behavioral sensitization produced by MPD involves the same neuronal mechanisms as amphetamine and cocaine. More importantly, chronic administration of MPD may also result in cross-sensitization with other psychostimulants. Methylphenidate is widely used to treat attention deficit/hyperactivity disorder (ADHD). The objectives of this study are to determine whether early exposure to MPD in juvenile rats increases their sensitivity to the drug when they are adult rats and whether treatment with MPD in juvenile and adult rats produces cross-sensitization to amphetamine. The study will consist of (1) monitoring the locomotor activity of two strains of rats (a model of ADHD and its control) before and after acute and repeated MPD administration when the rats are young and as adults followed by an amphetamine treatment and (2) evaluating sensory evoked potentials before and after drug treatment in freely moving rats with electrodes implanted in brain regions believed to be involved with ADHD, behavioral sensitization, and cross-sensitization.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Predoctoral Individual National Research Service Award (F31)
Project #
Application #
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Hoffman, Allison
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Health Science Center Houston
Schools of Medicine
United States
Zip Code
Chelaru, Mircea I; Yang, Pamela B; Dafny, Nachum (2012) Sex differences in the behavioral response to methylphenidate in three adolescent rat strains (WKY, SHR, SD). Behav Brain Res 226:8-17
Bergheim, M; Yang, P B; Burau, K D et al. (2012) Adolescent rat circadian activity is modulated by psychostimulants. Brain Res 1431:35-45
Yang, Pamela B; Atkins, Kristal D; Dafny, Nachum (2011) Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in female SD rats. Eur J Pharmacol 661:72-85
Yang, Pamela B; Cuellar 3rd, Derly O; Swann, Alan C et al. (2011) Age and genetic strain differences in response to chronic methylphenidate administration. Behav Brain Res 218:206-17
Algahim, Mohame Fodhl; Yang, Pamela Boi; Burau, Keith Dean et al. (2010) Repetitive ritalin treatment modulates the diurnal activity pattern of young SD male rats. Cent Nerv Syst Agents Med Chem 10:247-57
Yang, P B; Swann, A C; Dafny, N (2010) Psychostimulants given in adolescence modulate their effects in adulthood using the open field and the wheel-running assays. Brain Res Bull 82:208-17
Yang, Pamela B; Swann, Alan C; Dafny, Nachum (2007) Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization. Brain Res 1145:66-80
Yang, Pamela B; Swann, Alan C; Dafny, Nachum (2006) Sensory-evoked potentials recordings from the ventral tegmental area, nucleus accumbens, prefrontal cortex, and caudate nucleus and locomotor activity are modulated in dose-response characteristics by methylphenidate. Brain Res 1073-1074:164-74
Yang, Pamela B; Swann, Alan C; Dafny, Nachum (2006) Chronic methylphenidate modulates locomotor activity and sensory evoked responses in the VTA and NAc of freely behaving rats. Neuropharmacology 51:546-56
Dafny, Nachum; Yang, Pamela B (2006) The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 68:393-405

Showing the most recent 10 out of 15 publications