Evidence for the sensitivity of operant timing behaviour to stimulation of D1 dopamine receptors.
BACKGROUND
Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Previous studies using the fixed-interval peak procedure implicated D(2)-like dopamine receptors in these effects. However, recent findings suggest that d-amphetamine alters timing performance on the free-operant psychophysical procedure via D(1)-like receptors. It is not known whether this effect of d-amphetamine is mimicked by direct D(1)-like receptor stimulation.


OBJECTIVE
The effects of a D(1)-like receptor agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine (SKF-81297) on performance on the free-operant psychophysical procedure and the interaction between SKF-81297 and a D(1)-like receptor antagonist 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566) and a D(2)-like receptor antagonist haloperidol, were examined.


METHODS
Rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data (percent responding on B [%B] vs time from trial onset [t]) under each treatment condition, and quantitative indices of timing (T(50) [value of t corresponding to %B = 50] and the Weber fraction [(T(75)-T(25))/2T(50); T(25) and T(75) are values of t corresponding to %B = 25 and %B = 75] were compared among treatments.


RESULTS
SKF-81297 (0.8 mg kg(-1)) reduced T(50); this effect was antagonized by SKF-83566 (0.03 mg kg(-1)) but not by haloperidol (0.05, 0.1 mg kg(-1)).


CONCLUSIONS
Stimulation of D(1)-like dopamine receptors affects performance in the free-operant psychophysical procedure.
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D011594:Psychometrics; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013998:Time Perception / Q000187:drug effects*
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C067113:SK&F 81297; C044846:SKF83566