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EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans

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Abstract

Rationale

An involvement of 5-HT1A receptors is postulated in the pathophysiology of affective disorders and mechanism of action of antidepressants. Methods for studying their functional integrity in humans are, however, limited. Preliminary data suggests that activation of somatodendritic 5-HT1A receptors cause a negative shift in the EEG frequency spectrum. Animal research suggests that pindolol is an agonist at these receptors but an antagonist at postsynaptic 5-HT1A receptors.

Objective

We postulated that while pindolol would antagonise known postsynaptic mediated neuroendocrine responses to the 5-HT1A agonist buspirone, both drugs would have a similar effect on the EEG frequency spectrum.

Methods

Fourteen healthy men were administered placebo or pindolol (20 mg orally) 90 min before placebo or buspirone (30 mg orally) in a double blind cross-over study. Plasma prolactin and growth hormone were assayed and EEGs recorded before and after drug administration.

Results

A significant negative shift in the EEG frequency spectrum was found for both buspirone and pindolol, with the combination producing a similar effect to each drug alone. In contrast, the neuroendocrine response to buspirone was significantly attenuated by pindolol.

Conclusions

The data obtained are consistent with the EEG effects of buspirone and pindolol being mediated by somatodendritic 5-HT1A receptors, in contrast to the neuroendocrine response, which is known to be mediated by postsynaptic receptors. The development of this novel method of assessing somatodendritic 5-HT1A receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants.

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Acknowledgements

The authors would like to thank Richard Marsh for technical assistance during this project. They would also like to thank Professors I.N. Ferrier and C.H. Ashton for helpful discussions throughout the development of the techniques and Professors I.N. Ferrier, A.H. Young and C.D. Ingram and Dr S. Gartside for helpful comments on the manuscript. This study was funded by means of a Medical Research Council (UK) Clinician Scientist Fellowship award to R.H.McA-W.

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Authors and Affiliations

  1. Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle, Newcastle upon Tyne, NE1 4LP, UK

    R. H. McAllister-Williams & A. E. Massey

  2. Department of Psychiatry, Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK

    R. H. McAllister-Williams

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  1. R. H. McAllister-Williams
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  2. A. E. Massey
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Correspondence to R. H. McAllister-Williams.

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McAllister-Williams, R.H., Massey, A.E. EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans. Psychopharmacology 166, 284–293 (2003). https://doi.org/10.1007/s00213-002-1339-0

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