EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans.
BACKGROUND
An involvement of 5-HT(1A) 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-HT(1A) 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-HT(1A) receptors.


OBJECTIVE
We postulated that while pindolol would antagonise known postsynaptic mediated neuroendocrine responses to the 5-HT(1A) 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-HT(1A) 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-HT(1A) receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants.
McAllister-Williams
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RH
Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle, NE1 4LP, Newcastle upon Tyne, UK. r.h.mcallister-williams@ncl.ac.uk
Massey
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AE
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D002065:Buspirone / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D008297:Male; D010869:Pindolol / Q000009:adverse effects / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D019382:Human Growth Hormone; D011388:Prolactin; D010869:Pindolol; D002065:Buspirone