Acute handling stress modulates methylphenidate-induced catecholamine overflow in the medial prefrontal cortex.
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.
Marsteller
Douglas A
DA
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Gerasimov
Madina R
MR
Schiffer
Wynne K
WK
Geiger
Justin M
JM
Barnett
Channing R
CR
Schaich Borg
Jana
J
Scott
Sabria
S
Ceccarelli
Jill
J
Volkow
Nora D
ND
Molina
Patricia E
PE
Alexoff
David L
DL
Dewey
Stephen L
SL
D000208:Acute Disease; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006234:Handling, Psychological; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D002395:Catecholamines; D008774:Methylphenidate; D004298:Dopamine; D009638:Norepinephrine