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Somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptor function in major depression as assessed using the shift in electroencephalographic frequency spectrum with buspirone

Published online by Cambridge University Press:  01 July 2013

R. H. McAllister-Williams*
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
H. A. Alhaj
Academic Clinical Psychiatry, University of Sheffield, UK
A. Massey
Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
J. Pankiv
Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
U. Reckermann
Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
*Address for correspondence: R. H. McAllister-Williams, Academic Psychiatry, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 6BE, UK. (Email:



Positron emission tomography and post-mortem studies of the number of somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptors in raphé nuclei have found both increases and decreases in depression. However, recent genetic studies suggest they may be increased in number and/or function. The current study examined the effect of buspirone on the electroencephalographic (EEG) centroid frequency, a putative index of somatodendritic 5-HT1A receptor functional status, in a cohort of medication-free depressed patients and controls.


A total of 15 depressed patients (nine male) and intelligence quotient (IQ)-, gender- and age-matched healthy controls had resting EEG recorded from 29 scalp electrodes prior to and 30, 60 and 90 min after oral buspirone (30 mg) administration. The effect of buspirone on somatodendritic 5-HT1A receptors was assessed by calculating the EEG centroid frequency between 6 and 10.5 Hz. The effect of buspirone on postsynaptic 5-HT1A receptors was assessed by measuring plasma growth hormone, prolactin and cortisol concentrations.


Analysis of variance revealed a significantly greater effect of buspirone on the EEG centroid frequency in patients compared with controls (F1,28 = 6.55, p = 0.016). There was no significant difference in the neuroendocrine responses between the two groups.


These findings are consistent with an increase in the functional status of somatodendritic, but not postsynaptic, 5-HT1A autoreceptors, in medication-free depressed patients in line with hypotheses based on genetic data. This increase in functional status would be hypothesized to lead to an increase in serotonergic negative feedback, and hence decreased release of 5-HT at raphé projection sites, in depressed patients.

Original Articles
Copyright © Cambridge University Press 2013 

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Albert, PR, Le Francois, B, Millar, AM (2011). Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Molecular Brain 4, 21.CrossRefGoogle ScholarPubMed
Albert, PR, Zhou, QY, Van Tol, HH, Bunzow, JR, Civelli, O (1990). Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. Journal of Biological Chemistry 265, 58255832.Google ScholarPubMed
Alhaj, H, Wisniewski, G, McAllister-Williams, RH (2011). The use of the EEG in measuring therapeutic drug action: focus on depression and antidepressants. Journal of Psychopharmacology 25, 11751191.CrossRefGoogle Scholar
Alhaj, HA, Massey, AE, McAllister-Williams, RH (2007). A study of the neural correlates of episodic memory and HPA axis status in drug-free depressed patients and healthy controls. Journal of Psychiatric Research 41, 295304.CrossRefGoogle ScholarPubMed
Anderer, P, Barbanoj, MJ, Saletu, B, Semlitsch, HV (1993). Restriction to a limited set of EEG-target variables may lead to misinterpretation of pharmaco-EEG results. Neuropsychobiology 27, 112116.CrossRefGoogle ScholarPubMed
Anderer, P, Saletu, B, Pascual-Marqui, RD (2000). Effect of the 5-HT1A partial agonist buspirone on regional brain electrical activity in man: a functional neuroimaging study using low-resolution electromagnetic tomography (LORETA). Psychiatry Research 100, 8196.CrossRefGoogle Scholar
Arango, V, Underwood, MD, Boldrini, M, Tamir, H, Kassir, SA, Hsiung, S, Chen, JJ, Mann, JJ (2001). Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 25, 892903.CrossRefGoogle ScholarPubMed
Aznavour, N, Benkelfat, C, Gravel, P, Aliaga, A, Rosa-Neto, P, Bedell, B, Zimmer, L, Descarries, L (2009). MicroPET imaging of 5-HT1A receptors in rat brain: a test–retest [18F]MPPF study. European Journal of Nuclear Medicine and Molecular Imaging 36, 5362.CrossRefGoogle ScholarPubMed
Barbanoj, MJ, Anderer, P, Antonijoan, RM, Torrent, J, Saletu, B, Jané, F (1994). Topographical pharmaco-EEG mapping of increasing doses of buspirone and its comparison with diazepam. Human Psychopharmacology 9, 101109.CrossRefGoogle Scholar
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.CrossRefGoogle ScholarPubMed
Bel, N, Artigas, F (1992). Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study. European Journal of Pharmacology 229, 101103.CrossRefGoogle Scholar
Bhagwagar, Z, Rabiner, EA, Sargent, PA, Grasby, PM, Cowen, PJ (2004). Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Molecular Psychiatry 9, 386392.CrossRefGoogle Scholar
Blier, P, de Montigny, C (1994). Current advances in the treatment of depression. Trends in Pharmacological Sciences 15, 220226.CrossRefGoogle ScholarPubMed
Blier, P, Seletti, B, Gilbert, F, Young, SN, Benkelfat, C (2002). Serotonin 1A receptor activation and hypothermia in humans: lack of evidence for a presynaptic mediation. Neuropsychopharmacology 27, 301308.CrossRefGoogle ScholarPubMed
Bogdanov, NN, Bogdanov, MB (1994). The role of 5-HT1A serotonin and D2 dopamine receptors in buspirone effects on cortical electrical activity in rats. Neuroscience Letters 177, 14.CrossRefGoogle ScholarPubMed
Boldrini, M, Underwood, MD, Mann, JJ, Arango, V (2008). Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides. Journal of Psychiatric Research 42, 433442.CrossRefGoogle ScholarPubMed
Briggs, GG, Nebes, RD (1975). Patterns of hand preference in a student population. Cortex 11, 230238.CrossRefGoogle Scholar
Clifford, EM, Gartside, SE, Umbers, V, Cowen, PJ, Hajos, M, Sharp, T (1998). Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo . British Journal of Pharmacology 124, 206212.CrossRefGoogle ScholarPubMed
Cowen, PJ (2000). Psychopharmacology of 5-HT1A receptors. Nuclear Medicine and Biology 27, 437439.CrossRefGoogle Scholar
Czesak, M, Lemonde, S, Peterson, EA, Rogaeva, A, Albert, PR (2006). Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. Journal of Neuroscience 26, 18641871.CrossRefGoogle ScholarPubMed
Deakin, JFW, Graeff, FG (1991). 5-HT and mechanisms of defence. Journal of Psychopharmacology 5, 305315.CrossRefGoogle ScholarPubMed
Drevets, WC, Frank, E, Price, JC, Kupfer, DJ, Holt, D, Greer, PJ, Huang, Y, Gautier, C, Mathis, C (1999). PET imaging of serotonin 1A receptor binding in depression. Biological Psychiatry 46, 13751387.CrossRefGoogle ScholarPubMed
Drevets, WC, Thase, ME, Moses-Kolko, EL, Price, J, Frank, E, Kupfer, DJ, Mathis, C (2007). Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nuclear Medicine and Biology 34, 865877.CrossRefGoogle ScholarPubMed
Fekedulegn, DB, Andrew, ME, Burchfiel, CM, Violanti, JM, Hartley, TA, Charles, LE, Miller, DB (2007). Area under the curve and other summary indicators of repeated waking cortisol measurements. Psychosomatic Medicine 69, 651659.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (1997). Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version. Biometrics Research: New York.Google Scholar
Goodyer, IM, Herbert, J, Altham, PM, Pearson, J, Secher, SM, Shiers, HM (1996). Adrenal secretion during major depression in 8- to 16-year-olds, I. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation. Psychological Medicine 26, 245256.CrossRefGoogle Scholar
Hamilton, M (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278296.CrossRefGoogle ScholarPubMed
Hirvonen, J, Karlsson, H, Kajander, J, Lepola, A, Markkula, J, Rasi-Hakala, H, Nagren, K, Salminen, JK, Hietala, J (2008). Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. International Journal of Neuropsychopharmacology 11, 465476.CrossRefGoogle Scholar
Hjorth, S, Sharp, T (1991). Effect of the 5-HT1A receptor agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis. Life Sciences 48, 17791786.CrossRefGoogle ScholarPubMed
Holland, RL, Wesnes, K, Dietrich, B (1994). Single dose human pharmacology of umespirone. European Journal of Clinical Pharmacology 46, 461468.CrossRefGoogle ScholarPubMed
Kelly, JS, Larkman, P, Penington, NJ, Rainnie, DG, McAllister-Williams, H, Hodgkiss, J (1991). Serotonin receptor heterogeneity and the role of potassium channels in neuronal excitability. Advances in Experimental Medicine and Biology 287, 177191.CrossRefGoogle ScholarPubMed
Lesch, KP, Mayer, S, Disselkamp-Tietze, J, Hoh, A, Schoellnhammer, G, Schulte, HM (1990). Sub-sensitivity of the 5-hydroxytryptamine1A (5-HT1A) receptor mediated hypothermic response to ipsapirone in unipolar depression. Life Sciences 46, 12711277.CrossRefGoogle Scholar
Marrosu, F, Fornal, CA, Metzler, CW, Jacobs, BL (1996). 5-HT1A agonists induce hippocampal theta activity in freely moving cats: role of presynaptic 5-HT1A receptors. Brain Research 739, 192200.CrossRefGoogle ScholarPubMed
Martin, KF, Phillips, I, Hearson, M, Prow, MR, Heal, DJ (1992). Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants. British Journal of Pharmacology 107, 1521.CrossRefGoogle ScholarPubMed
McAllister-Williams, RH, Ferrier, IN, Young, AH (1998). Mood and neuropsychological function in depression: the role of corticosteroids and serotonin. Psychological Medicine 28, 573584.CrossRefGoogle ScholarPubMed
McAllister-Williams, RH, Kelly, JS (1995). The modulation of calcium channel currents recorded from adult rat dorsal raphe neurones by 5-HT1A receptor or direct G-protein activation. Neuropharmacology 34, 14911506.CrossRefGoogle ScholarPubMed
McAllister-Williams, RH, Massey, AE (2003). EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans. Psychopharmacology 166, 284293.CrossRefGoogle ScholarPubMed
McAllister-Williams, RH, Massey, AE, Fairchild, G (2007). Repeated cortisol administration attenuates the EEG response to buspirone in healthy volunteers: evidence for desensitization of the 5-HT1A autoreceptor. Journal of Psychopharmacology 21, 826832.CrossRefGoogle ScholarPubMed
Meltzer, CC, Price, JC, Mathis, CA, Butters, MA, Ziolko, SK, Moses-Kolko, E, Mazumdar, S, Mulsant, BH, Houck, PR, Lopresti, BJ, Weissfeld, LA, Reynolds, CF (2004). Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology 29, 22582265.CrossRefGoogle ScholarPubMed
Meltzer, HY, Maes, M (1994). Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects. Biological Psychiatry 35, 316323.CrossRefGoogle ScholarPubMed
Meltzer, HY, Maes, M (1995). Effects of ipsapirone on plasma cortisol and body temperature in major depression. Biological Psychiatry 38, 450457.CrossRefGoogle ScholarPubMed
Montgomery, SA, Asberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.CrossRefGoogle ScholarPubMed
Murasaki, M, Miura, S, Ishigooka, J, Ishii, Y, Takahashi, A, Fukuyama, Y (1989). Phase I study of a new antianxiety drug, buspirone. Progress in Neuro-psychopharmacology and Biological Psychiatry 13, 137144.CrossRefGoogle ScholarPubMed
Navinés, R, Gómez-Gil, E, Martín-Santos, R, de Osaba, MJ, Escolar, G, Gastó, C (2007). Hormonal response to buspirone is not impaired in major depression. Human Psychopharmacology 22, 389395.CrossRefGoogle Scholar
Nitz, DA, McNaughton, BL (1999). Hippocampal EEG and unit activity responses to modulation of serotonergic median raphe neurons in the freely behaving rat. Learning and Memory 6, 153167.Google ScholarPubMed
Parsey, RV, Ogden, RT, Miller, JM, Tin, A, Hesselgrave, N, Goldstein, E, Mikhno, A, Milak, M, Zanderigo, F, Sullivan, GM, Oquendo, MA, Mann, JJ (2010). Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations. Biological Psychiatry 68, 170178.CrossRefGoogle Scholar
Parsey, RV, Oquendo, MA, Ogden, RT, Olvet, DM, Simpson, N, Huang, YY, Van Heertum, RL, Arango, V, Mann, JJ (2006). Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biological Psychiatry 59, 106113.CrossRefGoogle Scholar
Saletu, B, Grunberger, J, Linzmayer, L (1986). On central effects of serotonin re-uptake inhibitors: quantitative EEG and psychometric studies with sertraline and zimelidine. Journal of Neural Transmission 67, 241266.CrossRefGoogle ScholarPubMed
Sargent, PA, Kjaer, KH, Bench, CJ, Rabiner, EA, Messa, C, Meyer, J, Gunn, RN, Grasby, PM, Cowen, PJ (2000). Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Archives of General Psychiatry 57, 174180.CrossRefGoogle Scholar
Savitz, J, Lucki, I, Drevets, WC (2009). 5-HT1A receptor function in major depressive disorder. Progress in Neurobiology 88, 1731.CrossRefGoogle ScholarPubMed
Seifritz, E, Moore, P, Trachsel, L, Bhatti, T, Stahl, SM, Gillin, JC (1996). The 5-HT1A agonist ipsapirone enhances EEG slow wave activity in human sleep and produces a power spectrum similar to 5-HT2 blockade. Neuroscience Letters 209, 4144.CrossRefGoogle ScholarPubMed
Semlitsch, HV, Anderer, P, Schuster, P, Presslich, O (1986). A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology 23, 695703.CrossRefGoogle ScholarPubMed
Stockmeier, CA, Shapiro, LA, Dilley, GE, Kolli, TN, Friedman, L, Rajkowska, G (1998). Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression – postmortem evidence for decreased serotonin activity. Journal of Neuroscience 18, 73947401.Google ScholarPubMed
Vertes, RP, Kinney, GG, Kocsis, B, Fortin, WJ (1994). Pharmacological suppression of the median raphe nucleus with serotonin1A agonists, 8-OH-DPAT and buspirone, produces hippocampal theta rhythm in the rat. Neuroscience 60, 441451.CrossRefGoogle ScholarPubMed
Vickers, AJ, Altman, DG (2001). Statistics notes: analysing controlled trials with baseline and follow up measurements. British Medical Journal 323, 11231124.CrossRefGoogle ScholarPubMed
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Somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptor function in major depression as assessed using the shift in electroencephalographic frequency spectrum with buspirone
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