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Evidence for a role of D1 dopamine receptors in d-amphetamine’s effect on timing behaviour in the free-operant psychophysical procedure

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Abstract

Rationale

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.

Materials and 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 [T 50 (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 T 50; 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.

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Notes

  1. Most drugs acting at D1 dopamine receptors do not discriminate between D1 and D5 dopamine receptors and are therefore, more precisely designated D1-like receptor agonists and antagonists. Similarly, most drugs acting at D2 receptors do not discriminate between D2, D3 and D4 receptors and are therefore, designated D2-like receptor agonists and antagonists (Seeman and van Tol 1994; Strange 2001). Throughout this paper, for the sake of simplicity, they are referred to as D1 and D2 receptor agonists and antagonists.

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Acknowledgements

This work was supported by the BBSRC. We are grateful to Ms. V. K. Bak and Mr. R. W. Langley for skilled technical help.

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Authors and Affiliations

  1. Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen’s Medical Centre Nottingham, Nottingham, NG7 2UH, UK

    T. H. C. Cheung, G. Bezzina, K. Asgari, S. Body, C. M. Bradshaw & E. Szabadi

  2. School of Biomedical Sciences, University of Nottingham, Nottingham, UK

    K. C. F. Fone

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  1. T. H. C. Cheung
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Correspondence to C. M. Bradshaw.

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Cheung, T.H.C., Bezzina, G., Asgari, K. et al. Evidence for a role of D1 dopamine receptors in d-amphetamine’s effect on timing behaviour in the free-operant psychophysical procedure. Psychopharmacology 185, 378–388 (2006). https://doi.org/10.1007/s00213-006-0339-x

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