Abstract
Understanding the neurochemistry of anxiety is of fundamental importance in the development and use of novel anxiolytics. Through measuring peripheral markers of brain biochemistry, direct pharmacological challenges and brain neuroimaging techniques our understanding of this field has increased substantially in the past few decades. We review the four most studied neurotransmitter systems with respect to in anxiety disorders: gamma amino-butyric acid, serotonin, noradrenaline and dopamine. We have focussed upon clinical studies to highlight the current techniques used to determine brain neurochemistry in vivo. Future research in this field will greatly benefit from recent advances in neuroimaging techniques and the discovery of novel ligands targeting specific receptors.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC (1991) Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatry 48:157–162
Abelson JL, Curtis GC, Uhde TW (2005) Twenty-four hour growth hormone secretion in patients with panic disorder. Psychoneuroendocrinology 30:72–79
Alvarenga ME, Richards JC, Lambert G, Esler MD (2006) Psychophysiological mechanisms in panic disorder: a correlative analysis of noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis of heart rate variability, and psychological variables. Psychosom Med 68:8–16
Argyropoulos SV, Nutt DJ (2003) Neurochemical aspects of anxiety. In: Nutt DJ, Ballenger J (eds) Anxiety disorders. Blackwell, Oxford, pp 183–199 Chapter 11
Argyropoulos SV, Hood SD, Adrover M, Bell CJ, Rich AS, Nash JR, Rich NC, Witchel HJ, Nutt DJ (2004) Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Biol Psychiatry 56:503–509
Baldwin DS, Polkinghorn C (2005) Evidence-based pharmacotherapy of Generalized Anxiety Disorder. Int J Neuropsychopharmacol 8:293–302
Bell C, Forshall S, Adrover M, Nash J, Hood S, Argyropoulos S, Rich A, Nutt DJ (2002) Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine. J Psychopharmacol 16:5–14
Bergink V, Westenberg HG (2005) Metabotropic glutamate II receptor agonists in panic disorder: a double blind clinical trial with LY354740. Int Clin Psychopharmacol 20:291–293
Bergink V, van Megen HJ, Westenberg HG (2004) Glutamate and anxiety. Eur Neuropsychopharmacol 14:175–183
Berrios GE, Campbell C, Politynska BE (1995) Autonomic failure, depression and anxiety in Parkinson’s disease. Br J Psychiatry 166:789–792
Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004) Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 84:835–867
Billinton A, Ige AO, Wise A, White JH, Disney GH, Marshall FH, Waldvogel HJ, Faull RL, Emson PC (2000) GABA(B) receptor heterodimer-component localisation in human brain. Brain Res Mol Brain Res 77:111–124
Blier P, de Montigny C, Chaput Y (1990) A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. J Clin Psychiatry 51(Suppl):14–20 discussion 21:14–20
Bormann J (2000) The ‘ABC’ of GABA receptors. Trends Pharmacol Sci 21:16–19
Bremner JD, Innis RB, Southwick SM, Staib L, Zoghbi S, Charney DS (2000a) Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Am J Psychiatry 157:1120–1126
Bremner JD, Innis RB, White T, Fujita M, Silbersweig D, Goddard AW, Staib L, Stern E, Cappiello A, Woods S, Baldwin R, Charney DS (2000b) SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder. Biol Psychiatry 47:96–106
Brown MJ, Jenner DA, Allison DJ, Dollery CT (1981) Variations in individual organ release of noradrenaline measured by an improved radioenzymatic technique; limitations of peripheral venous measurements in the assessment of sympathetic nervous activity. Clin Sci (Lond) 61:585–590
Cameron OG, Huang GC, Nichols T, Koeppe RA, Minoshima S, Rose D, Frey KA (2007) Reduced gamma-aminobutyric acid(A)-benzodiazepine binding sites in insular cortex of individuals with panic disorder. Arch Gen Psychiatry 64:793–800
Cartmell J, Schoepp DD (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 75:889–907
Chang L, Cloak CC, Ernst T (2003) Magnetic resonance spectroscopy studies of GABA in neuropsychiatric disorders. J Clin Psychiatry 64(Suppl 3):7–14
Charney DS, Heninger GR (1986) Abnormal regulation of noradrenergic function in panic disorders. Effects of clonidine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry 43:1042–1054
Charney DS, Heninger GR, Breier A (1984) Noradrenergic function in panic anxiety. Effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry 41:751–763
Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology (Berl) 92:14–24
Choy Y, Peselow ED, Case BG, Pressman MA, Luff JA, Laje G, Paizis M, Ying P, Guardino MT (2007) Three-year medication prophylaxis in panic disorder: to continue or discontinue? A naturalistic study. Compr Psychiatry 48:419–425
Cortelli P, Avallone R, Baraldi M, Zeneroli ML, Mandrioli J, Corsi L, Riva R, Tinuper P, Lugaresi E, Baruzzi A, Montagna P (2005) Endozepines in recurrent stupor. Sleep Med Rev 9:477–487
Cryan JF, Kaupmann K (2005) Don’t worry ‘B’ happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 26:36–43
de Haas SL, de Visser SJ, van der Post JP, Schoemaker RC, van Dyck K, Murphy MG, de Smet M, Vessey LK, Ramakrishnan R, Xue L, Cohen AF, van Gerven JM (2008) Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABA(A) alpha2, 3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers. J Psychopharmacol 22:24–32
Denys D, van der Wee N, Janssen J, de Geus F, Westenberg HG (2004) Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder. Biol Psychiatry 55:1041–1045
Dorow R, Horowski R, Paschelke G, Amin M (1983) Severe anxiety induced by FG 7142, a beta-carboline ligand for benzodiazepine receptors. Lancet 2:98–99
Dunayevich E, Erickson J, Levine L, Landbloom R, Schoepp DD, Tollefson GD (2008) Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder. Neuropsychopharmacology 33:1603–1610
Eriksson E, Westberg P, Alling C, Thuresson K, Modigh K (1991) Cerebrospinal fluid levels of monoamine metabolites in panic disorder. Psychiatry Res 36:243–251
Eser D, Baghai TC, Moller HJ (2007) Evidence of agomelatine’s antidepressant efficacy: the key points. Int Clin Psychopharmacol 22(Suppl 2):S15–S19
Farrant M, Nusser Z (2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6:215–229
Feltner D, Wittchen HU, Kavoussi R, Brock J, Baldinetti F, Pande AC (2008) Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 23:18–28
Fritschy JM, Benke D, Mertens S, Oertel WH, Bachi T, Mohler H (1992) Five subtypes of type A gamma-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies. Proc Natl Acad Sci USA 89:6726–6730
Gao B, Hornung JP, Fritschy JM (1995) Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex. Neuroscience 65:101–117
Garvey MJ, Noyes R Jr, Woodman C, Laukes C (1995) The association of urinary 5-hydroxyindoleacetic acid and vanillylmandelic acid in patients with generalized anxiety. Neuropsychobiology 31:6–9
Gentil V, Tavares S, Gorenstein C, Bello C, Mathias L, Gronich G, Singer J (1990) Acute reversal of flunitrazepam effects by Ro 15–1788 and Ro 15–3505: inverse agonism, tolerance, and rebound. Psychopharmacology (Berl) 100:54–59
George DT, Nutt DJ, Rawlings RR, Phillips MJ, Eckardt MJ, Potter WZ, Linnoila M (1995) Behavioral and endocrine responses to clomipramine in panic disorder patients with or without alcoholism. Biol Psychiatry 37:112–119
Geuze E, van Berckel BN, Lammertsma AA, Boellaard R, de Kloet CS, Vermetten E, Westenberg HG (2008) Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder. Mol Psychiatry 13:74–83
Goddard AW, Mason GF, Appel M, Rothman DL, Gueorguieva R, Behar KL, Krystal JH (2004) Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. Am J Psychiatry 161:2186–2193
Goldberg MR, Hollister AS, Robertson D (1983) Influence of yohimbine on blood pressure, autonomic reflexes, and plasma catecholamines in humans. Hypertension 5:772–778
Goodman WK, McDougle CJ, Price LH (1992) The role of serotonin and dopamine in the pathophysiology of obsessive compulsive disorder. Int Clin Psychopharmacol 7(Suppl 1):35–38
Graeff FG, Guimaraes FS, De Andrade TG, Deakin JF (1996) Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54:129–141
Griebel G, Perrault G, Sanger DJ (1997) A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety. Neuropharmacology 36:793–802
Grillon C, Cordova J, Levine LR, Morgan CA III (2003) Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl) 168:446–454
Habib KE, Weld KP, Rice KC, Pushkas J, Champoux M, Listwak S, Webster EL, Atkinson AJ, Schulkin J, Contoreggi C, Chrousos GP, McCann SM, Suomi SJ, Higley JD, Gold PW (2000) Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates. Proc Natl Acad Sci USA 97:6079–6084
Hein L, Altman JD, Kobilka BK (1999) Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature 402:181–184
Hollander E, DeCaria C, Nitescu A, Cooper T, Stover B, Gully R, Klein DF, Liebowitz MR (1991) Noradrenergic function in obsessive-compulsive disorder: behavioral and neuroendocrine responses to clonidine and comparison to healthy controls. Psychiatry Res 37:161–177
Hood SD, Bell CJ, Nutt DJ (2005) Acute tryptophan depletion. Part I: rationale and methodology. Aust N Z J Psychiatry 39:558–564
Hood SD, Potokar JP, Davies SJ, Hince DA, Morris K, Seddon KM, Nutt DJ, Argyropoulos SV (2006) Dopaminergic challenges in social anxiety disorder. Abstract number: S.15.02, Papers of the 19th ECNP Congress, European Neuropsychopharmacology 16 (Suppl 4):S186
Javitt DC (2004) Glutamate as a therapeutic target in psychiatric disorders. Molecular Psychiatry 9:984–997, 979
Johnson MR, Lydiard RB, Zealberg JJ, Fossey MD, Ballenger JC (1994) Plasma and CSF HVA levels in panic patients with comorbid social phobia. Biol Psychiatry 36:425–427
Johnson PL, Lightman SL, Lowry CA (2004) A functional subset of serotonergic neurons in the rat ventrolateral periaqueductal gray implicated in the inhibition of sympathoexcitation and panic. Ann N Y Acad Sci 1018:58–64
Kalueff A, Nutt DJ (1996) Role of GABA in memory and anxiety. Depress Anxiety 4:100–110
Kalueff AV, Nutt DJ (2007) Role of GABA in anxiety and depression. Depress Anxiety 24:495–517
Kaschka W, Feistel H, Ebert D (1995) Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil SPECT. J Psychiatr Res 29:427–434
Ko GN, Elsworth JD, Roth RH, Rifkin BG, Leigh H, Redmond DE Jr (1983) Panic-induced elevation of plasma MHPG levels in phobic-anxious patients. Effects of clonidine and imipramine. Arch Gen Psychiatry 40:425–430
Korpi ER, Sinkkonen ST (2006) GABA(A) receptor subtypes as targets for neuropsychiatric drug development. Pharmacol Ther 109:12–32
Kotlinska J, Liljequist S (1998) A characterization of anxiolytic-like actions induced by the novel NMDA/glycine site antagonist, L-701, 324. Psychopharmacology (Berl) 135:175–181
Kuikka JT, Pitkanen A, Lepola U, Partanen K, Vainio P, Bergstrom KA, Wieler HJ, Kaiser KP, Mittelbach L, Koponen H et al (1995) Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder. Nucl Med Commun 16:273–280
Lambert E, Hotchkin E, Alvarenga M, Pier C, Richards J, Barton D, Dawood T, Esler M, Lambert G (2006) Single-unit analysis of sympathetic nervous discharges in patients with panic disorder. J Physiol 570:637–643
Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien LK, Holik A, Attarbaschi T, Mossaheb N, Sacher J, Geiss-Granadia T, Kletter K, Kasper S, Tauscher J (2007) Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61:1081–1089
Liebowitz MR, Schneier F, Campeas R, Hollander E, Hatterer J, Fyer A, Gorman J, Papp L, Davies S, Gully R (1992) Phenelzine vs atenolol in social phobia. A placebo-controlled comparison. Arch Gen Psychiatry 49:290–300
Longone P, Rupprecht R, Manieri GA, Bernardi G, Romeo E, Pasini A (2008) The complex roles of neurosteroids in depression and anxiety disorders. Neurochem Int 52:596–601
Louie AK, Lannon RA, Ketter TA (1989) Treatment of cocaine-induced panic disorder. Am J Psychiatry 146:40–44
Maes M, Van GA, Delmeire L, Kenis G, Bosmans E, Song C (2002) Platelet alpha 2-adrenoceptor density in humans: relationships to stress-induced anxiety, psychasthenic constitution, gender and stress-induced changes in the inflammatory response system. Psychol Med 32:919–928
Malizia AL (2002) Receptor binding and drug modulation in anxiety. Eur Neuropsychopharmacol 12:567–574
Malizia AL, Cunningham VJ, Bell CJ, Liddle PF, Jones T, Nutt DJ (1998) Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. Arch Gen Psychiatry 55:715–720
Millan MJ (2005) Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie 60:441–460
Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, Dekeyne A, Nicolas JP, Lejeune F (2000) Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram. Eur J Neurosci 12:1079–1095
Munjack DJ, Crocker B, Cabe D, Brown R, Usigli R, Zulueta A, McManus M, McDowell D, Palmer R, Leonard M (1989) Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. J Clin Psychopharmacol 9:22–27
Munjack DJ, Baltazar PL, DeQuattro V, Sobin P, Palmer R, Zulueta A, Crocker B, Usigli R, Buckwalter G, Leonard M (1990) Generalized anxiety disorder: some biochemical aspects. Psychiatry Res 32:35–43
Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, Grasby PM, Nutt DJ (2008) A positron emission tomography study of serotonin 5-HT1A receptor availability in untreated and recovered patients with panic disorder. Br J Psychiatry 193:1–6
Nayeem N, Green TP, Martin IL, Barnard EA (1994) Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis. J Neurochem 62:815–818
Nemeroff CB (2003) The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull 37:133–146
Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, Eckelman W, Herscovitch P, Charney DS, Drevets WC (2004) Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 24:589–591
Nielsen M, Braestrup C, Squires RF (1978) Evidence for a late evolutionary appearance of brain-specific benzodiazepine receptors: an investigation of 18 vertebrate and 5 invertebrate species. Brain Res 141:342–346
Nutt DJ (1986) Increased central alpha 2-adrenoceptor sensitivity in panic disorder. Psychopharmacology (Berl) 90:268–269
Nutt DJ (1989) Altered central alpha 2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiatry 46:165–169
Nutt DJ (2001) The pharmacology of human anxiety. In: Griez E, Faravelli C, Nutt DJ, Zohar J (eds) Anxiety disorders. Wiley, Chichester, pp 309–324 Chapter 16
Nutt DJ (2003) Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol 17:355–364
Nutt D (2006) GABAA receptors: subtypes, regional distribution, and function. J Clin Sleep Med 2:S7–S11
Nutt D, Lawson C (1992) Panic attacks. A neurochemical overview of models and mechanisms. Br J Psychiatry 160:165–178
Nutt DJ, Malizia AL (2001) New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry 179:390–396
Ohishi H, Shigemoto R, Nakanishi S, Mizuno N (1993) Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J Comp Neurol 335:252–266
Olsen RW, Chang CS, Li G, Hanchar HJ, Wallner M (2004) Fishing for allosteric sites on GABA(A) receptors. Biochem Pharmacol 68:1675–1684
Orser BA (2006) Extrasynaptic GABAA receptors are critical targets for sedative-hypnotic drugs. J Clin Sleep Med 2:S12–S18
Pillay NS, Stein DJ (2007) Emerging anxiolytics. Expert Opin Emerg Drugs 12:541–554
Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G (2000) GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101:815–850
Plaznik A, Palejko W, Nazar M, Jessa M (1994) Effects of antagonists at the NMDA receptor complex in two models of anxiety. Eur Neuropsychopharmacol 4:503–512
Pollack MH, Jensen JE, Simon NM, Kaufman RE, Renshaw PF (2008) High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam. Prog Neuropsychopharmacol Biol Psychiatry 32:739–743
Rapaport MH, Clary C, Fayyad R, Endicott J (2005) Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry 162:1171–1178
Rasmusson AM, Anderson GM, Lynch KA, McSwiggan-Hardin M, Scahill LD, Mazure CM, Goodman WK, Price LH, Cohen DJ, Leckman JF (1997) A preliminary study of tryptophan depletion on tics, obsessive-compulsive symptoms, and mood in Tourette’s syndrome. Biol Psychiatry 41:117–121
Roy-Byrne PP, Geraci M, Uhde TW (1986) Life events and the onset of panic disorder. Am J Psychiatry 143:1424–1427
Roy-Byrne PP, Cowley DS, Greenblatt DJ, Shader RI, Hommer D (1990) Reduced benzodiazepine sensitivity in panic disorder. Arch Gen Psychiatry 47:534–538
Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 8:1–27
Rupprecht R, Eser D, Zwanzger P, Moller HJ (2006) GABAA receptors as targets for novel anxiolytic drugs. World J Biol Psychiatry 7:231–237
Sandford JJ, Argyropoulos SV, Nutt DJ (2000) The psychobiology of anxiolytic drugs. Part 1: basic neurobiology. Pharmacol Ther 88:197–212
Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS (2003) A placebo-controlled trial of risperidone in Tourette syndrome. Neurology 60:1130–1135
Schank JR, Liles LC, Weinshenker D (2008) Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety. Biol Psychiatry 63:1007–1012
Schlegel S, Steinert H, Bockisch A, Hahn K, Schloesser R, Benkert O (1994) Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report. Eur Arch Psychiatry Clin Neurosci 244:49–51
Schneier FR, Liebowitz MR, Abi-Dargham A, Zea-Ponce Y, Lin SH, Laruelle M (2000) Low dopamine D(2) receptor binding potential in social phobia. Am J Psychiatry 157:457–459
Schneier FR, Martinez D, Abi-Dargham A, Zea-Ponce Y, Simpson HB, Liebowitz MR, Laruelle M (2008) Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings. Depress Anxiety 25:1–7
Schoepp DD, Wright RA, Levine LR, Gaydos B, Potter WZ (2003) LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 6:189–197
Schruers K, Griez E (2004) The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder. J Psychopharmacol 18:553–558
Sheehan DV, Raj AB, Sheehan KH, Soto S (1990) Is buspirone effective for panic disorder? J Clin Psychopharmacol 10:3–11
Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M, Flor PJ, Neki A, Abe T, Nakanishi S, Mizuno N (1997) Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 17:7503–7522
Shlik J, Aluoja A, Vasar V, Vasar E, Podar T, Bradwejn J (1997) Effects of citalopram treatment on behavioural, cardiovascular and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder. J Psychiatry Neurosci 22:332–340
Sieghart W (1995) Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev 47:181–234
Sinclair LI, Christmas DM, Hood SD, Potokar JP, Robertson A, Isaac A, Srivastava S, Nutt DJ, Davies SJ (2009) Antidepressant-induced jitteriness/anxiety syndrome: systematic review. Br J Psychiatry 194:483–490
Stanford SC, Salmon P (1989) Neurochemical correlates of behavioural responses to frustrative nonreward in the rat: implications for the role of central noradrenergic neurones in behavioural adaptation to stress. Exp Brain Res 75:133–138
Szabo ST, Blier P (2001) Response of the norepinephrine system to antidepressant drugs. CNS Spectr 6:679–684
Tancer ME, Stein MB, Uhde TW (1993) Growth hormone response to intravenous clonidine in social phobia: comparison to patients with panic disorder and healthy volunteers. Biol Psychiatry 34:591–595
Tancer ME, Mailman RB, Stein MB, Mason GA, Carson SW, Golden RN (1994) Neuroendocrine responsivity to monoaminergic system probes in generalized social phobia. Anxiety 1:216–223
Targum SD (1990) Differential responses to anxiogenic challenge studies in patients with major depressive disorder and panic disorder. Biol Psychiatry 28:21–34
Tauscher J, Bagby RM, Javanmard M, Christensen BK, Kasper S, Kapur S (2001) Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers. Am J Psychiatry 158:1326–1328
Tiihonen J, Kuikka J, Bergstrom K, Lepola U, Koponen H, Leinonen E (1997a) Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry 154:239–242
Tiihonen J, Kuikka J, Rasanen P, Lepola U, Koponen H, Liuska A, Lehmusvaara A, Vainio P, Kononen M, Bergstrom K, Yu M, Kinnunen I, Akerman K, Karhu J (1997b) Cerebral benzodiazepine receptor binding and distribution in generalized anxiety disorder: a fractal analysis. Mol Psychiatry 2:463–471
Trendelenburg AU, Starke K, Limberger N (1994a) Presynaptic alpha 2A-adrenoceptors inhibit the release of endogenous dopamine in rabbit caudate nucleus slices. Naunyn Schmiedebergs Arch Pharmacol 350:473–481
Trendelenburg AU, Trendelenburg M, Starke K, Limberger N (1994b) Release-inhibiting alpha 2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with alpha 2-autoreceptors. Naunyn Schmiedebergs Arch Pharmacol 349:25–33
Uhde TW, Stein MB, Vittone BJ, Siever LJ, Boulenger JP, Klein E, Mellman TA (1989) Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder. Arch Gen Psychiatry 46:170–177
Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 95:3239–3244
van VI, Westenberg HG, den Boer JA (1996) Effects of the 5-HT1A receptor agonist flesinoxan in panic disorder. Psychopharmacology (Berl) 127:174–180
Whiting PJ, Bonnert TP, McKernan RM, Farrar S, Le Bourdelles B, Heavens RP, Smith DW, Hewson L, Rigby MR, Sirinathsinghji DJ, Thompson SA, Wafford KA (1999) Molecular and functional diversity of the expanding GABA-A receptor gene family. Ann N Y Acad Sci 868:645–653
WHO (2000) Cross-national comparisons of the prevalences and correlates of mental disorders. WHO International Consortium in Psychiatric Epidemiology. Bull World Health Organ 78:413–426
Williams K, Argyropoulos S, Nutt DJ (2000) Amphetamine misuse and social phobia. Am J Psychiatry 157:834–835
Wittchen HU, Jacobi F (2005) Size and burden of mental disorders in Europe–a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 15:357–376
Wu LJ, Kim SS, Zhuo M (2008) Molecular targets of anxiety: from membrane to nucleus. Neurochem Res 33:1925–1932
Ziegler MG, Lake CR, Wood JH, Brooks BR, Ebert MH (1977) Relationship between norepinephrine in blood and cerebrospinal fluid in the presence of a blood-cerebrospinal fluid barrier for norepinephrine. J Neurochem 28:677–679
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Durant, C., Christmas, D., Nutt, D. (2009). The Pharmacology of Anxiety. In: Stein, M., Steckler, T. (eds) Behavioral Neurobiology of Anxiety and Its Treatment. Current Topics in Behavioral Neurosciences, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2009_8
Download citation
DOI: https://doi.org/10.1007/7854_2009_8
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-02911-0
Online ISBN: 978-3-642-02912-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)