1. Buspirone and Pindolol Effects on the EEG Frequency Spectrum in Healthy Men R.H. McAllister-Williams* and A.E. Massey Department of Psychiatry, University of Newcastle, Newcastle upon Tyne, UK Introduction l 5-HT 1A receptors may be of central importance in the pathophysiology and treatment of affective disorders 1 l Current methods of examining their functional integrity in man are limited: F The neuroendocrine response to l-tryptophan and 5-HT 1A agonists may reflect postsynaptic hypothalamic 5-HT 1A receptor activation 2 F The hypothermic effect of 5-HT 1A agonists is believed to reflect a combination of somatodendritic and postsynaptic 5- HT 1A receptor activation 3 l The 5-HT 1A agonist buspirone causes a leftward shift of the EEG frequency spectrum 4,5 which is hypothesised to reflect somatodendritic 5-HT 1A receptor activation Methods l 14 healthy male volunteers l 4-way random order cross over, double blind experiment l Resting EEG recorded, plus temperature, prolactin levels and VAS for ‘depressed’, ‘drowsy’, ‘restless’, ‘nausea’ and ‘lightheaded’ EEG Temp Blood VAS 01:302:002:303:00 EEG Temp Blood VAS EEG Temp Blood VAS EEG Temp Blood VAS Pindolol 20 mg or placebo Buspirone 30 mg or placebo l 10 min EEG recording : F 29 scalp electrodes F referenced to left mastoid, re- referenced off-line to linked mastoids F band width 0.1 - 100 Hz F blink corrected using VEOG F 10 s epochs generated F rejected if voltage deflection >  75  V (including HEOG) F FFT generated with bin width of 0.1 Hz F Post-hoc analysis used 8 colored sites to examine ant/post and left/right differences Subjects 1 2 l Prolactin response to buspirone and pindolol l Main effect of drug (F(1.7,26.3) = 15.80, p < 0.001) l Main effect of buspirone (F(1.0,20.7) = 27.85, p < 0.001) l Trend for effect of pindolol (F(1.0,16.6) = 4.61, p = 0.053) l Pindolol + buspirone significantly less than buspirone (F(1.0,18.6) = 20.07, p < 0.001) 3 l Temperature response to buspirone and pindolol l Main effect of drug (F(2.0,60.0) = 6.30, p < 0.01) l Main effect of buspirone (F(1.3,30.8) = 7.65, p < 0.05) l Main effect of pindolol (F(1.3,31.6) = 6.67, p < 0.05) l Pindolol + buspirone not significantly different to buspirone alone l Subjective effects rated using VAS scales l Nomain effect of buspirone or pindolol on depressed, drowsy or restless VAS l Significant buspirone X time effect, but not pindolol, on ‘nausea’ (F(2.52,30.23) = 4.86, p < 0.01) and ‘lightheaded’(F(2.06,26.82) = 10.32, p < 0.001) l Pindolol + buspirone significantly less than buspirone (F(2.26,27.11) = 4.80, p < 0.05 and F(2.42,29.08) = 3.03, p = 0.055 respectively) 4 l Buspirone and pindolol effects on the EEG frequency spectrum F Relative power between 0.5 and 30Hz calculated from FFT (plotted to 15Hz) 5 6 l Frequency spectrum analysis by bands F Using bands determined by factor analysis 6 l Analysis of theta band F Drug X AP effect for buspirone (F(1,13) = 4.64, p = 0.051) and pindolol (F(1,13) = 18.24, p < 0.001) F No significant difference between pindolol+ buspirone and buspirone alone l Centroid analysis of FFT between 6 and 10.5 Hz Analysis of centroids - 8 sites 7 l Significant effect of buspirone and pindolol l Effect greater at posterior sites l Pindolol + buspirone not significantly different from buspirone alone Correlation between effects 8 l Weak correlation between shift in centroid (P7) and restlessness and prolactin response l Strongest correlation between prolactin response and nausea and lightheadedness Conclusions l Buspirone (30 mg) causes a leftward shift of the EEG frequency spectrum between 6 and 10.5 Hz in healthy subjects l Pindolol (20 mg) causes a similar effect l The relative effects of buspirone and pindolol on the EEG are different to the prolactin response which is known to reflect postsynaptic 5-HT 1A activation l Pindolol has been shown to be a partial agonist at somatodendritic 5-HT 1A receptors in rodents 7 l The shift in EEG spectrum with buspirone and pindolol may reflect somatodendritic 5-HT 1A receptor activation Acknowledgements l This work was supported by an MRC (UK) Clinician Scientist Fellowship award toRHMcAW References 1. 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