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Effects of 8-OH-DPAT and WAY-100635 on performance on a time-constrained progressive-ratio schedule

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Abstract

Rationale

Performance on progressive-ratio schedules has been proposed as a means of assessing the effects of drugs on motivation. We have adopted a mathematical model proposed by Killeen to analyse the effects of drugs acting at 5-HT1A receptors on progressive-ratio performance. According to this model, the relationship between response rate and ratio size is described by a bitonic (inverted-U) function. One parameter of the function, a, expresses the motivational or "activating" effect of the reinforcer (duration of activation of responding produced by the reinforcer), whereas another parameter, δ, expresses the minimum time needed to execute a response and is regarded as an index of "motor capacity".

Objective

To examine the effect of the selective 5-HT1A receptor agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] and the antagonist WAY-100635 [N-[2-(4-[2-methoxyphenyl]-1-piperazinyl)ethyl]-N-2-pyridinylcyclo-hexanecarboxamide] on progressive-ratio schedule performance.

Methods

Sixteen rats responded for a food-pellet reinforcer on a time-constrained progressive-ratio schedule (55-min sessions). In phase 1, they received single doses (s.c.) of 8-OH-DPAT (25, 50, 100, 200 μg kg−1, four treatments at each dose) or the vehicle (0.9% saline solution). In phase 2, they received WAY-100635 (30, 100, 300 μg kg−1) according to the same regimen. In phase 3, they received 8-OH-DPAT (100 μg kg−1) alone or in combination with WAY-100635 (30 μg kg−1). 8-OH-DPAT dose dependently increased the value of a, significant increases being seen with the 50, 100 and 200 μg kg−1 doses. The highest dose also increased δ. WAY-100635 did not significantly alter either a or δ. WAY-100635 significantly attenuated the effect of 8-OH-DPAT on both a and δ.

Conclusions

The results suggest that 8-OH-DPAT enhanced the activating effect of the reinforcer (the highest dose may also have induced motor debilitation). The finding that the effect of 8-OH-DPAT on a was attenuated by WAY-100635 implicates 5-HT1A receptors in this effect. The results are consistent with previous reports that 8-OH-DPAT facilitates feeding and food-reinforced operant responding in rats and suggest that these effects may be brought about by an increase in food motivation.

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Acknowledgements

This work was supported by the Wellcome Trust. We are grateful to Ms. V.K. Pincott 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

    M.-Y. Ho, S. Body, S. Kheramin, C. M. Bradshaw & E. Szabadi

  2. Institute of Clinical Behavioral Sciences, Chang Gung University, 333, Kwei Shan, Taiwan

    M.-Y. Ho

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  1. M.-Y. Ho
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  2. S. Body
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  3. S. Kheramin
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  4. C. M. Bradshaw
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  5. E. Szabadi
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Correspondence to C. M. Bradshaw.

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Ho, MY., Body, S., Kheramin, S. et al. Effects of 8-OH-DPAT and WAY-100635 on performance on a time-constrained progressive-ratio schedule. Psychopharmacology 167, 137–144 (2003). https://doi.org/10.1007/s00213-002-1375-9

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  • DOI: https://doi.org/10.1007/s00213-002-1375-9

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