Psychopharmacology

, Volume 179, Issue 2, pp 489–497 | Cite as

Quantitative analysis of the effects of some “atypical” and “conventional” antipsychotics on progressive ratio schedule performance

  • Z. Zhang
  • J. F. Rickard
  • K. Asgari
  • S. Body
  • C. M. Bradshaw
  • E. Szabadi
Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on the value or “efficacy” of reinforcers. A mathematical model affords a basis for quantifying the effects of drugs on progressive ratio schedule performance. According to this model, the relation 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”. In a previous experiment we found that the “atypical” antipsychotic clozapine increased a, indicating an increase in the efficacy of a food reinforcer.

Objective

We examined the effects of four “atypical” and four “conventional” antipsychotics on progressive ratio schedule performance.

Methods

Rats responded for a sucrose reinforcer (0.6 M, 50 μl) on a time-constrained progressive ratio schedule (50-min sessions). After 90 preliminary training sessions, they received acute doses of antipsychotics (doses in mg kg−1): atypical: clozapine (2, 4, 8, IP; n=15), quetiapine (1.25, 2.5, 5, 10, SC; n=23), olanzapine (0.25, 0.5, 1, IP; n=15), ziprasidone (0.625, 1.25, 2.5, IP, n=15); conventional: haloperidol (0.025, 0.05, 0.1, IP, n=15), pimozide (0.125, 0.25, 0.5, IP; n=15), raclopride (0.25, 0.5, 1, SC; n=12), cis-flupenthixol (0.2, 0.4, 0.8, SC; n=15). Values of a and δ were estimated from the response rate functions obtained under each treatment condition, and were compared between drug and vehicle-alone treatments.

Results

The atypical antipsychotics significantly increased a (indicating enhancement of reinforcer efficacy), and also increased δ (indicating reduction of motor capacity). Haloperidol, pimozide and raclopride significantly increased δ; none of the conventional antipsychotics significantly altered a.

Conclusions

The results extend previous findings with clozapine to other atypical antipsychotics and suggest that enhancement of the efficacy of reinforcers may be a common feature of atypical antipsychotics not shared by conventional antipsychotics.

Keywords

Progressive ratio schedule Antipsychotics Clozapine Quetiapine Olanzapine Ziprasidone Haloperidol Pimozide Raclopride Cis-flupenthixol Reinforcer efficacy 
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Notes

Acknowledgements

This work was supported by the Wellcome Trust (Travelling Fellowship awarded to Z.Z.). We are grateful to Ms. V.K. Bak for skilled technical help.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Z. Zhang
    • 1
  • J. F. Rickard
    • 1
  • K. Asgari
    • 1
  • S. Body
    • 1
  • C. M. Bradshaw
    • 1
  • E. Szabadi
    • 1
  1. 1.Psychopharmacology Section, Division of Psychiatry, Medical School, Queen’s Medical CentreUniversity of NottinghamNottinghamUK

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