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

Neuropsychopharmacology. 2002 Aug;27(2):163-70. doi: 10.1016/S0893-133X(02)00288-9.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adrenergic Uptake Inhibitors / pharmacology*
  • Animals
  • Catecholamines / metabolism*
  • Dopamine / metabolism
  • Drug Administration Schedule
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Handling, Psychological*
  • Male
  • Methylphenidate / pharmacology*
  • Microdialysis
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Norepinephrine / metabolism
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology


  • Adrenergic Uptake Inhibitors
  • Catecholamines
  • Methylphenidate
  • Dopamine
  • Norepinephrine