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Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors

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Abstract

Rationale

Operant timing behaviour is sensitive to dopaminergic manipulations. It has been proposed that this effect is mediated principally by D2-like dopamine receptors. However, we recently found that the effect of d-amphetamine on timing in the free-operant psychophysical procedure was mediated by D1-like dopamine receptors. It has not been established whether stimulation of D2-like receptors affects timing in this schedule.

Objective

To examine the effects of a D2-like receptor agonist quinpirole on second-range timing and the ability of dopamine receptor antagonists to reverse quinpirole’s effects.

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 rates [percent responding on B (%B) vs time (t)] under each treatment; quantitative timing indices [T 50 (value of t when %B = 50) and Weber fraction] were compared among treatments.

Results

Quinpirole (0.04, 0.08 mg kg−1) reduced T 50. This effect was attenuated by D2-like receptor antagonists haloperidol (0.05, 0.1 mg kg−1), eticlopride (0.04, 0.08 mg kg−1) and sulpiride (30, 60 mg kg−1), but not by the D3 receptor-preferring antagonist nafadotride (0.5, 1 mg kg−1), the D4 receptor antagonist L-745870 (1, 3 mg kg−1) or the D1-like receptor antagonist SKF-83566 (0.015 mg kg−1).

Conclusions

Results suggest that quinpirole reduced T 50 via an action at D2 receptors. D1-like and D2-like receptors may mediate behaviourally similar but pharmacologically distinct effects on timing behaviour.

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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, the terms D1-like and D2-like are used except where reference is made to the specific receptor type.

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Acknowledgements

This work was supported by the BBSRC. We are grateful to Ms. V. K. Bak 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, NG7 2UH, UK

    T. H. C. Cheung, G. Bezzina, C. L. Hampson, 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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  2. G. Bezzina
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  3. C. L. Hampson
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  4. S. Body
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Correspondence to C. M. Bradshaw.

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Cheung, T.H.C., Bezzina, G., Hampson, C.L. et al. Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors. Psychopharmacology 193, 423–436 (2007). https://doi.org/10.1007/s00213-007-0798-8

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