Evidence for a role of D1 dopamine receptors in d-amphetamine's effect on timing behaviour in the free-operant psychophysical procedure.
BACKGROUND
Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Studies using the fixed-interval peak procedure implicated D2 dopamine receptors in these effects. Less is known about the effects of dopaminergic manipulations on temporal differentiation in other timing schedules.


OBJECTIVE
To examine the effects of a D1 antagonist,8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566), and a D2 antagonist, haloperidol, on performance on the free-operant psychophysical procedure, and the ability of these antagonists to reverse the effects of the catecholamine-releasing agent, d-amphetamine on performance. The antagonists' ability to reverse d-amphetamine-induced hyperlocomotion was also examined.


METHODS
Rats responded on two levers (A and B) under a free-operant psychophysical schedule, in which reinforcement was provided intermittently for responding on A during the first half, and B during the second half, of 50-s trials. Logistic functions were fitted to the relative response rate data (percent responding on B [%B] vs time [t]) in each treatment condition, and quantitative timing indices [T50 (value of t corresponding to %B=50) and Weber fraction] were compared among treatments. Effects of the treatments on locomotion were measured in a separate experiment.


RESULTS
SKF-83566 (0.015, 0.03, 0.06 mg kg(-1)) did not affect timing performance. Haloperidol (0.025, 0.05 mg kg(-1)) had no effect; a higher dose (0.1 mg kg(-1)) reduced T (50). d-Amphetamine (0.4 mg kg(-1)) reduced T50; this effect was antagonised by SKF-83566 but not by haloperidol. Both antagonists reduced d-amphetamine-induced hyperlocomotion.


CONCLUSIONS
The results suggest that d-amphetamine's effect on performance in the free-operant psychophysical procedure is mediated by D1 rather than D2 receptors.
Cheung
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Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre Nottingham, Nottingham, NG7 2UH, UK.
Bezzina
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Szabadi
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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; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / 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; D003913:Dextroamphetamine; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C044846:SKF83566