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

• Published in: Psychopharmacologia Vol. 192; no. 2; pp. 193 - 206
• Main Authors: EAGLE, Dawn M, TUFFT, Miles R. A, GOODCHILD, Hannah L, ROBBINS, Trevor W
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-06-2007; Springer Nature B.V
• Subjects: Amphetamines; Animal behavior; Animals; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Behavior disorders; Behavior, Animal - drug effects; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - pharmacology; Biological and medical sciences; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Disease Models, Animal; Dopamine; Dopamine Antagonists - pharmacology; Dopamine D1 receptors; Dopamine D2 receptors; Dose-Response Relationship, Drug; Drug abuse; Flupenthixol; Flupenthixol - pharmacology; Impulsive Behavior; Inhibition, Psychological; Male; Medical sciences; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate - pharmacology; Modafinil; Motor ability; Neuropharmacology; Pharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psycholeptics: tranquillizer, neuroleptic; Psychology; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Rats; Reaction Time - drug effects; Reaction time task; Receptors, Dopamine - drug effects; Receptors, Dopamine - metabolism; Response time; Rodents; Side effects; Amphetamine derivatives; Response inhibition; Rat; SSRT; Thioxanthene derivatives; Hyperactivity; Neuroleptic; Psychotropic; Attentional disorder; Piperidine derivatives; d-amphetamine . ADHD; Attention disorder with hyperactivity; Inhibition; CNS stimulant; Dopamine receptor; Dopamine antagonist; Interaction; Rodentia; Vertebrata; Mammalia; D2 Dopamine receptor; Modafinil; Animal; Reaction time; Dexamfetamine; Flupentixol; Performance; Methylphenidate
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-007-0701-7

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.
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.
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.
This evidence supports a hypothesis that stop and go processes are under control of distinct neurochemical mechanisms.