Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol.
BACKGROUND
The stop-signal reaction time (SSRT) task measures inhibition of a response that has already been initiated, i.e. the ability to stop. 'Impulsive' human subjects, e.g. with attention deficit and hyperactivity disorder (ADHD), have longer SSRTs. Both SSRT and go-trial reaction time (GoRT) may be sensitive to drugs such as d-amphetamine, methylphenidate and modafinil, both in normal subjects and those with ADHD.


OBJECTIVE
To investigate the effects of modafinil (3, 10, 30 and 100 mg/kg) and methylphenidate (0.3, 1.0 and 3.0 mg/kg) on SSRT task performance in the rat. To investigate the possible contribution of dopamine receptors in the action of these drugs using the mixed D1/D2 dopamine receptor antagonist cis-flupenthixol.


RESULTS
Modafinil significantly decreased SSRT with little effect on GoRT but only in rats with slow baseline SSRTs. Fast SSRTs were not changed by modafinil. Methylphenidate decreased GoRTs of all rats. However, methylphenidate had baseline-dependent effects on SSRT, decreasing SSRT in slow responders but increasing SSRT in fast responders. Cis-flupenthixol (0.01, 0.04 and 0.125 mg/kg) had no effects on SSRT but increased GoRT at higher doses. At the lowest dose (0.01 mg/kg), cis-flupenthixol failed to disrupt the SSRT-decreasing effects of either modafinil or methylphenidate, whereas at 0.04 mg/kg, the cis-flupenthixol-dependent increase in GoRT was antagonised by methylphenidate but not by modafinil.


CONCLUSIONS
This evidence supports a hypothesis that stop and go processes are under control of distinct neurochemical mechanisms.
Eagle
Dawn M
DM
Department of Experimental Psychology, University of Cambridge, Downing Site, Cambridge, CB2 3EB, UK. d.eagle@psychol.cam.ac.uk
Tufft
Miles R A
MR
Goodchild
Hannah L
HL
Robbins
Trevor W
TW
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005475:Flupenthixol / Q000494:pharmacology; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D000077408:Modafinil; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D008774:Methylphenidate; D005475:Flupenthixol; D000077408:Modafinil