Acute handling stress modulates methylphenidate-induced catecholamine overflow in the medial prefrontal cortex

Douglas A. Marsteller, Madina R. Gerasimov, Wynne K. Schiffer, Justin M. Geiger, Channing R. Barnett, Jana Schaich Borg, Sabria Scott, Jill Ceccarelli, Nora D. Volkow, Patricia E. Molina, David L. Alexoff, Stephen L. Dewey

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Although stress is an extensively investigated phenomenon, the effects of specific stressors on the pharmacologic activity of routinely administered drugs are less well characterized. We designed the present study to investigate the effect of handling stress on catecholaminergic responsivity following an acute methylphenidate (MP, Ritalin) challenge in the medial prefrontal cortex (mPFC). Norepinephrine (NE) and dopamine (DA) levels were simultaneously measured in 15-min samples of PFC dialysate using HPLC coupled with electrochemical detection. Sprague-Dawley rats were handled for 15 min, which produced an increase from basal extracellular DA and NE levels. Handling stress attenuates the DA response when administered 2 h prior to IP MP, whereas handling stress enhances the DA response when administered simultaneously with IG MP. These findings suggest that persistent alterations in mesocorticolimbic DA-ergic activity are induced by a short exposure to restraint stress as evidenced by the altered response to MP challenge.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
Issue number2
StatePublished - 2002

Bibliographical note

Funding Information:
This research was carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886), and by the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155) and the National Institute on Drug Abuse (5RO-DA06278 and DA09490).


  • Dopamine
  • Handling stress
  • Medial prefrontal cortex
  • Methylphenidate
  • Microdialysis
  • Norepinephrine


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