Amphetamine decreases behavioral inhibition by stimulation of dopamine D2, but not D3, receptors.
Behavioral disinhibition is a manifestation of impulsive behavior that is prominent in the psychopathology of various psychiatric disorders such as addiction, attention-deficit hyperactivity disorder, mania, and personality disorders. Impulsivity may be studied by measuring anticipatory responses made before the presentation of a food-predictive, brief light stimulus in a two-choice serial reaction time task. In such serial reaction time tasks, amphetamine has been shown to produce dose-dependent increases in premature responding in a manner dependent on dopamine D(2)-like receptor stimulation. So far, it is unknown whether it is the D(2) or D(3) receptor that is involved in this form of impulsivity. In this study, rats were trained in a two-choice serial reaction time task until baseline performance was stable. Next, effects of the dopamine D(2) preferring antagonist L-741,626 and selective D(3) antagonist SB-277011 were assessed alone and in the presence of amphetamine. Neither L-741,626 nor SB-277011 affected behavioral inhibition, although the latter significantly increased reaction time at 10 mg/kg. Amphetamine dose-dependently increased impulsivity. The effect of amphetamine was attenuated by L-741,626 (3 mg/kg), whereas SB-277011 (3 mg/kg) had no effect. Therefore, amphetamine-induced behavioral disinhibition depends on D(2), but not D(3), receptor stimulation.
van Gaalen
Marcel M
MM
Neuroscience Research, GPRD, Abbott, Knollstrasse, Ludwigshafen, Germany. marcel.vangaalen@abbott.com
Unger
Liliane
L
Jongen-Rêlo
Ana-Lucia
AL
Schoemaker
Hans
H
Gross
Gerhard
G
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D009570:Nitriles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; C104750:3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole; D000661:Amphetamine