Abstract
The wide use of serotonin reuptake inhibitors and serotonin receptor agonists in anxiety disorders has suggested a key role for the modulatory neurotransmitter in anxiety. However, serotonin’s specific role is still uncertain. This article reviews the literature concerning how and where serotonergic agents modulate anxiety. Varying and sometimes conflicting data from human and animal studies argue for both anxiolytic and anxiogenic roles for serotonin, depending on the specific disorder, structure, or behavioral task studied. However, recent data from molecular genetic studies in the mouse point toward two important roles for the serotonin 1A receptor. In development, serotonin acts through this receptor to promote development of the circuitry necessary for normal anxiety-like behaviors. In adulthood, serotonin reuptake inhibitors act through the same receptor to stimulate neurogenesis and reduce anxiety-like behaviors. These studies highlight that the complex serotonin system likely plays various roles in the regulation of anxiety both during development and in adulthood.
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Alvarez, C., Vitalis, T., Fon, E. A., et al. (2002) Effects of genetic depletion of monoamines on somatosensory cortical development. Neuroscience 115, 753–764.
Andrade, R. (1998) Regulation of membrane excitability in the central nervous system by serotonin receptor subtypes. Ann. NY Acad. Sci. 861, 190–203.
Andrade, R., and Chaput, Y. (1991) 5-hydroxytryptamine4-like receptors mediate the slow excitatory response to serotonin in the rat hippocampus. J. Pharmacol. Exp. Ther. 257, 930–937.
Andrade, R., and Nicoll, R. A. (1987) Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro. J. Physiol. 394, 99–124.
Barr, L. C., Goodman, W. K., Mcdougle, C. J., et al. (1994) Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Arch. Gen. Psychiatry 51, 309–317.
Barr, L. C., Goodman, W. K., Price, L. H., Mcdougle, C. J., Charney, D. S. (1992) The serotonin hypothesis of obsessive compulsive disorder: Implications of pharmacologic challenge studies. J. Clin. Psychiatry 53(Suppl), 17–28.
Baumann, M. H., Mash, D. C., Staley, J. K. (1995) The serotonin agonist m-chlorophenylpiperazine (mcpp) binds to serotonin transporter sites in human brain. Neuroreport 6, 2150–2152.
Beckett, S., and Marsden, C. A. (1997) The effect of central and systemic injection of the 5-ht1a receptor agonist 8-ohdpat and the 5-ht1a receptor antagonist way 100635 on periaqueductal grey-induced defence behaviour. J. Psychopharmacol. 11, 35–40.
Beckett, S. R., Lawrence, A. J., Marsden, C. A., Marshall, P. W. (1992) Attenuation of chemically induced defence response by 5-ht1 receptor agonists administered into the periaqueductal gray. Psychopharmacol. (Berl.) 108, 110–114.
Bel, N., and Artigas, F. (1993) Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei. Synapse 15, 243–245.
Bel, N., and Artigas, F. (1999) Modulation of the extracellular 5-hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran. Microdialysis studies in rats. Neuropsychopharmacology 21, 745–754.
Bell, C., Abrams, J., Nutt, D. (2001) Tryptophan depletion and its implications for psychiatry. Br. J. Psychiatry 178, 399–405.
Bengel, D., Murphy, D. L., Andrews, A. M., et al. (1998) Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylene-dioxymethamphetamine (“ecstasy”) in serotonin transporter-deficient mice. Mol. Pharmacol. 53, 649–655.
Bodnoff, S. R., Suranyi-Cadotte, B., Aitken, D. H., Quirion, R., Meaney, M. J. (1988) The effects of chronic antidepressant treatment in an animal model of anxiety. Psychopharmacol. (Berl.) 95, 298–302.
Bodnoff, S. R., Suranyi-Cadotte, B., Quirion, R., Meaney, M. J. (1989) A comparison of the effects of diazepam versus several typical and atypical anti-depressant drugs in an animal model of anxiety. Psychopharmacol. (Berl.) 97, 277–279.
Brandao, M. L., Lopez-Garcia, J. A., Graeff, F. G., Roberts, M. H. (1991) Electrophysiological evidence for excitatory 5-ht2 and depressant 5-ht1a receptors on neurones of the rat midbrain tectum. Brain Res. 556, 259–266.
Carli, M., Tatarczynska, E., Cervo, L., Samanin, R. (1993) Stimulation of hippocampal 5-ht1a receptors causes amnesia and anxiolytic-like but not antidepressant-like effects in the rat. Eur. J. Pharmacol. 234, 215–221.
Cases, O., Self, I., Grimsby, J., et al. (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOa. Science 268, 1763–1766.
Cases, O., Vitalis, T., Seif, I., De Maeyer, E., Sotelo, C., Gaspar, P. (1996) Lack of barrels in the somatosensory cortex of monoamine oxidase a-deficient mice: role of a serotonin excess during the critical period. Neuron 16, 297–307.
Charney, D. S., and Drevets, W. C. (2002) The neurobiological basis of anxiety disorders. In Davis, K. L., D. S. Charney, J. T. Coyle, and C. Nemeroff (eds.). Neuropsychopharmacology: The fifth generation of progress, Lippincott Williams and Wilkins, Philadelphia, pp. 901–930.
Chen, L., He, M., Sibille, E., et al. (1999) Adaptive changes in postsynaptic dopamine receptors despite unaltered dopamine dynamics in mice lacking monoamine oxidase b. J. Neurochem. 73, 647–655.
Coyle, J. T., and Duman, R. S. (2003) Finding the intracellular signaling pathways affected by mood disorder treatments. Neuron 38, 157–160.
Deckert, J., Catalano, M., Syagailo, Y. V., et al. (1999) Excess of high activity monoamine oxidase a gene promoter alleles in female patients with panic disorder. Hum. Mol. Genet. 8, 621–624.
D’sa, C., and Duman, R. S. (2002) Antidepressants and neuroplasticity. Bipolar Disord. 4, 183–194.
Evrard, A., Malagie, I., Laporte, A. M., et al. (2002) Altered regulation of the 5-ht system in the brain of mao-a knock-out mice. Eur. J. Neurosci. 15, 841–851.
Fabre, V., Beaufour, C., Evrard, A., et al. (2000) Altered expression and functions of serotonin 5-ht1a and 5-ht1b receptors in knock-out mice lacking the 5-ht transporter. Eur. J. Neurosci. 12, 2299–2310.
File, S. E., and Gonzalez, L. E. (1996a) Anxiolytic effects in the plus-maze of 5-ht1a-receptor ligands in dorsal raphe and ventral hippocampus. Pharmacol. Biochem. Behav. 54, 123–128.
File, S. E., Gonzalez, L. E., Andrews, N. (1996b) Comparative study of pre- and postsynaptic 5-ht1a receptor modulation of anxiety in two ethological animal tests. J. Neurosci. 16, 4810–4815.
Frisch, A., Michaelovsky, E., Rockah, R., et al. (2000) Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways. Eur. Neuropsychopharmacol. 10, 205–209.
Fuller, R. W. (1994) Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci. 55, 163–167.
Germine, M., Goddard, A. W., Sholomskas, D. E., Woods, S. W., Charney, D. S., Heninger, G. R. (1994) Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: Influence of reduction in intravenous dosage. Psychiatry Res. 54, 115–133.
Gingrich, J. A. (2002) Mutational analysis of the serotonergic system: Recent findings using knockout mice. Curr. Drug Target CNS Neurol. Disord. 1, 449–465.
Gobbi, G., Murphy, D. L., Lesch, K., Blier, P. (2001) Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study. J. Pharmacol. Exp. Ther. 296, 987–995.
Goddard, A. W., Charney, D. S., Germine, M., et al. (1995) Effects of tryptophan depletion on responses to yohimbine in healthy human subjects. Biol. Psychiatry 38, 74–85.
Gorman, J. M., Hirschfeld, R. M., Ninan, P. T. (2002a) New developments in the neurobiological basis of anxiety disorders. Psychopharmacol. Bull. 36(Suppl 2), 49–67.
Gorman, J. M., Kent, J. M., Coplan, J. D. (2002b) Current and emerging therapeutics of anxiety and stress disorders. In Davis, K. L., D. S. Charney, J. T. Coyle and C. Nemeroff (eds.). Neuropsychopharmacology: The fifth generation of progress, Lippincott Williams & Wilkins, Philadelphia, pp. 967–980.
Gould, E. (1999) Serotonin and hippocampal neurogenesis. Neuropsychopharmacology 21, 46S-51S.
Graeff, F. G., Viana, M. B., Mora, P. O. (1997) Dual role of 5-ht in defense and anxiety. Neurosci. Biobehav. Rev. 21, 791–799.
Gray, J. A., and Mcnaughton, N. (2000) The neuropsychology of anxiety. In The neuropsychology of anxiety, (2nd ed.). Oxford University Press, New York.
Greenberg, B. D., Tolliver, T. J., Huang, S. J., Li, Q., Bengel, D., Murphy, D. L. (1999) Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am. J. Med. Genet. 88, 83–87.
Griebel, G. (1995) 5-hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmacol. Therap. 65, 319–395.
Griebel, G., Moreau, J. L., Jenck, F., Misslin, R., Martin, J. R. (1994) Acute and chronic treatment with 5-ht reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents. Psychopharmacol. (Berl.) 113, 463–470.
Groenink, L., Pattij, T., De Jongh, R., et al. (2003) 5-ht(1a) receptor knockout mice and mice over-expressing corticotropin-releasing hormone in models of anxiety. Eur. J. Pharmacol. 463, 185–3197.
Gross, C., Zhuang, X., Stark, K., et al. (2002) Serotonin1a receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416, 396–400.
Gustavsson, J. P., Nothen, M. M., Jonsson, E. G., et al. (1999) No association between serotonin transporter gene polymorphisms and personality traits. Am. J. Med. Genet. 88, 430–436.
Hamilton, S. P., Heiman, G. A., Haghighi, F., et al. (1999) Lack of genetic linkage or association between a functional serotonin transporter polymorphism and panic disorder. Psychiatric Genet. 9, 1–6.
Hamilton, S. P., Slager, S. L., Heiman, G. A., et al. (2000) No genetic linkage or association between a functional promoter polymorphism in the monoamine oxidase-a gene and panic disorder. Mol. Psychiatry 5, 465–466.
Hashimoto, S., Inoue, T., Koyama T. (1996) Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing behavior in rats. Psychopharmacol. (Berl.) 123, 182–186.
Heisler, L. K., Chu, H. M., Brennan, T. J., et al. (1998) Elevated anxiety and antidepressant-like responses in serotonin 5-ht1a receptor mutant mice. Proc. Natl. Acad. Sci. USA. 95, 15049–15054.
Hendricks, T., Francis, N., Fyodorov, D., Deneris, E. S. (1999) The ets domain factor pet-1 is an early and precise marker of central serotonin neurons and interacts with a conserved element in serotonergic genes. J. Neurosci. 19, 10348–10356.
Hendricks, T. J., Fyodorov, D. V., Wegman, L. J., et al. (2003) Pet-1 ets gene plays a critical role in 5-ht neuron development and is required for normal anxiety-like and aggressive behavior. Neuron 37, 233–247.
Hollander, E., Kwon, J., Weiller, F., et al. (1998) Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects. Psychiatry Res. 79, 213–217.
Holmes, A., Murphy, D. L., Crawley, J. N. (2002) Reduced aggression in mice lacking the serotonin transporter. Psychopharmacol. (Berl.). 161, 160–167.
Hoyer, D., Hannon, J. P., Martin, G. R. (2002) Molecular, pharmacological and functional diversity of 5-ht receptors. Pharmacol. Biochem. Behav. 71, 533–554.
Inoue, T., Hashimoto, S., Tsuchiya, K., Izumi, T., Ohmori, T., Koyama, T. (1996) Effect of citalopram, a selective serotonin reuptake inhibitor, on the acquisition of conditioned freezing. Eur. J. Pharmacol. 311, 1–6.
Johnson, M. R., and Lydiard, R. B. (1995) The neurobiology of anxiety disorders. Psychiatr. Clin. North Am. 18, 681–725.
Jorm, A. F., Henderson, A. S., Jacomb, P. A., et al. (1998) An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms. Mol. Psychiatry. 3, 449–451.
Katsuragi, S., Kunugi, H., Sano, A., et al. (1999) Association between serotonin transporter gene polymorphism and anxiety-related traits. Biol. Psychiatry 45, 368–370.
Kendler, K. S., Walters, E. E., Neale, M. C., Kessler, R. C., Heath, A. C., Eaves, L. J. (1995) The structure of the genetic and environmental risk factors for six major psychiatric disorders in women. Phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Arch. Gen. Psychiatry. 52, 374–3383.
Kessler, R. C., and Greenberg, P. E. (2002) The economic burden of anxiety and stress disorders. In Davis, K. L., D. S. Charney, J. T. Coyle and C. Nemeroff (eds.), Neuropsychopharmacology: The fifth generation of progress, Lippincott Williams & Wilkins, Philadelphia, pp. 981–992.
Kim, J. J., Shih, J. C., Chen, K., et al. (1997) Selective enhancement of emotional, but not motor, learning in monoamine oxidase a-deficient mice. Proc. Natl. Acad. Sci. USA. 94, 5929–5933.
Klaassen, T., Klumperbeek, J., Deutz, N. E. P., Van Praag, H. M., Griez, E. (1998) Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge. Psychiatry Res. 77, 167–174.
Kostowski, W., Plaznik, A., Stefanski, R. (1989) Intra-hippocampal buspirone in animal models of anxiety. Eur. J. Pharmacol. 168, 393–3396.
Kreiss, D. S., and Lucki, I. (1995) Effects of acute and repeated administration of antidepressant drugs on extracellular levels of 5-hydroxytryptamine measured in vivo. J. Pharmacol. Exp. Ther. 274, 8663–876.
Kurt, M., Arik, A. C., Celik, S. (2000) The effects of sertraline and fluoxetine on anxiety in the elevated plus-maze test in mice. J. Basic Clin. Physiol. Pharmacol. 11, 173–180.
Lee, K., Dixon, A. K., Pinnock, R. D. (1999) Serotonin depolarizes hippocampal interneurones in the rat stratum oriens by interaction with 5ht2 receptors. Neurosci. Lett. 270, 56–358.
Lesch, K. P. (2001) Molecular foundation of anxiety disorders. J. Neural Transm. 108, 717–746.
Lesch, K. P., Bengel, D., Heils, A., et al. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531.
Li, Q., Wichems, C. H., Ma, L., Van De Kar, L. D., Garcia, F., Murphy, D. L. (2003) Brain region-specific alterations of 5-ht2a and 5-ht2c receptors in serotonin transporter knockout mice. J. Neurochem. 84, 1256–1265.
Lira, A., Zhou, M., Castanon, N., et al. Altered dorsal raphé function and depression-related behaviors in serotonin transporter deficient mice altered depression and anxiety-related behaviors and impaired serotonergic function in serotonin transporter deficient mice. Biol. Psychiatry. 754, 960–971.
Malberg, J. E., Eisch, A. J., Nestler, E. J., Duman, R. S. (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 20, 9104–9110.
Mann, J. J., Huang, Y. Y., Underwood, M. D., et al. (2000) A serotonin transporter gene promoter polymorphism (5-httlpr) and prefrontal cortical binding in major depression and suicide. Arch. Gen. Psychiatry 57, 729–738.
Matsuo, M., Kataoka, Y., Mataki, S., Kato, Y., Oi, K. (1996) Conflict situation increases serotonin release in rat dorsal hippocampus: In vivo study with microdialysis and Vogel test. Neurosci. Lett. 215, 197–200.
Millan, M. J., and Brocco, M. (2003) The Vogel conflict test: procedural aspects, gamma-aminobutyric acid, glutamate and monoamines. Eur. J. Pharmacol. 463, 67–96.
Miller, H. E., Deakin, J. F., Anderson, I. M. (2000) Effect of acute tryptophan depletion on co2-induced anxiety in patients with panic disorder and normal volunteers. Br. J. Psychiatry. 176, 182–188.
Mossner, R., Albert, D., Persico, A. M., et al. (2000) Differential regulation of adenosine a(1) and a(2a) receptors in serotonin transporter and monoamine oxidase a-deficient mice. Eur. Neuropsychopharmacol. 10, 489–493.
Naylor, L., Dean, B., Pereira, A., Mackinnon, A., Kouzmenko, A., Copolov, D. (1998) No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. Mol. Med. 4, 671–674.
Njung’e, K., and Handley, S. L. (1991) Effects of 5-ht uptake inhibitors, agonists and antagonists on the burying of harmless objects by mice; a putative test for anxiolytic agents. Br. J. Pharmacol. 104, 105–112.
Nogueira, R. L., and Graeff, F. G. (1995) Role of 5-ht receptor subtypes in the modulation of dorsal periaqueductal gray generated aversion. Pharmacol. Biochem. Behav. 52, 1–6.
Nunes-De-Souza, R. L., Canto-De-Souza, A., Rodgers, R. J. (2002) Effects of intra-hippocampal infusion of way-100635 on plus-maze behavior in mice. Influence of site of injection and prior test experience. Brain Res. 927, 87–396.
Parks, C. L., Robinson, P. S., Sibille, E., Shenk, T., Toth, M. (1998) Increased anxiety of mice lacking the serotonin1a receptor. Proc. Natl. Acad. Sci. USA. 95, 10734–10739.
Pattij, T., Groenink, L., Oosting, R. S., Van Der Gugten, J., Maes, R. A., Olivier, B. (2002) Gaba(a)-benzodiazepine receptor complex sensitivity in 5-ht(1a) receptor knockout mice on a 129 / sv background. Eur. J. Pharmacol. 447, 67–74.
Porter, R. H., Benwell, K. R., Lamb, H., et al. (1999) Functional characterization of agonists at recombinant human 5-ht2a, 5-ht2b and 5-ht2c receptors in cho-k1 cells. Br. J. Pharmacol. 128, 13–20.
Przegalinski, E., Tatarczynska, E., Klodzinska, A., Chojnacka-Wojcik, E. (1994) The role of postsynaptic 5-ht1a receptors in the anticonflict effect of ipsapirone. Neuropharmacology 33, 1109–1115.
Rabiner, E. A., Messa, C., Sargent, P. A., et al. (2002) A database of [11c]way-100635 binding to 5-ht1a receptors in normal male volunteers: normative data and relationship to methodological, demographic, physiological, and behavioral variables. NeuroImage 15, 620–632.
Radley, J. J., and Jacobs, B. L. (2002) 5-ht1a receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res. 955, 264–267.
Ramboz, S., Oosting, R., Amara, D. A., et al. (1998) Serotonin receptor 1a knockout: an animal model of anxiety-related disorder. Proc. Natl. Acad. Sci. USA. 95, 14476–14481.
Rebsam, A., Seif, I., Gaspar, P. (2002) Refinement of thalamocortical arbors and emergence of barrel domains in the primary somatosensory cortex: a study of normal and monoamine oxidase a knockout mice. J. Neurosci 22, 8541–8552.
Ropert, N., and Guy, N. (1991) Serotonin facilitates GABA-ergic transmission in the ca1 region of rat hippocampus in vitro. J. Physiol. 441, 121–136.
Salichon, N., Gaspar, P., Upton, A. L., et al. (2001) Excessive activation of serotonin (5-ht) 1b receptors disrupts the formation of sensory maps in monoamine oxidase a and 5-ht transporter knock-out mice. J. Neurosci. 21, 884–896.
Santarelli, L., Saxe, M., Gross, C., et al. (2003) Hippocampal neurogenesis contributes to the behavioral effects of antidepressants. Science 301, 805–809.
Schoeffter, P., and Hoyer, D. (1989) Interaction of arylpiperazines with 5-ht1a, 5-ht1b, 5-ht1c and 5-ht1d receptors: Do discriminatory 5-ht1b receptor ligands exist? Naunyn Schmiedebergs Arch. Pharmacol. 339, 675–683.
Schruers, K., Van Diest, R., Overbeek, T., Griez, E. (2002) Acute l-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. 113, 237–243.
Shen, R. Y., and Andrade, R. (1998) 5-hydroxytryptamine2 receptor facilitates GABA-ergic neurotransmission in rat hippocampus. J. Pharmacol. Exp. Ther. 285, 805–812.
Shih, J. C., Ridd, M. J., Chen, K., et al. (1999) Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase a. Brain Res. 835, 104–112.
Sibille, E., Pavlides, C., Benke, D., Toth, M. (2000) Genetic inactivation of the serotonin(1a) receptor in mice results in downregulation of major gaba(a) receptor alpha subunits, reduction of gaba(a) receptor binding, and benzodiazepine-resistant anxiety. J. Neurosci. 20, 2758–2765.
Silva, R. C., and Brandao, M. L. (2000) Acute and chronic effects of gepirone and fluoxetine in rats tested in the elevated plus-maze: an ethological analysis. Pharmacol. Biochem. Behav. 65, 209–216.
Smeraldi, E., Diaferia, G., Erzegovesi, S., Lucca, A., Bellodi, L., Moja, E. A. (1996) Tryptophan depletion in obsessive-compulsive patients. Biol. Psychiatry 40, 398–402.
Stefanski, R., Palejko, W., Bidzinski, A., Kostowski, W., Plaznik, A. (1993) Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of midazolam and 5-ht1a receptor agonists. Neuropharmacology 32, 977–985.
Stein, L., Wise, C. D., Berger, B. D. (1973) Anti-anxiety action of benzodiazepines: decrease in activity of serotonin neurons in the punishment system. In Soubrie, P. (ed.). Animal models in psychiatric disorders (3rd ed.) Karger, Basel, pp. 48–67.
Tauscher, J., Bagby, R. M., Javanmard, M., Christensen, B. K., 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, 1326–31328.
Toth, M. (2003) 5-ht(1a) receptor knockout mouse as a genetic model of anxiety. Eur. J. Pharmacol. 463, 177–184.
Viana, M. B., Tomaz, C., Graeff, F. G. (1994) The elevated t-maze: a new animal model of anxiety and memory. Pharmacol. Biochem. Behav. 49, 549–3554.
Vogel, J. R., Beer, B., Clody, D. E. (1971) A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacologia 21, 1–37.
Whitton, P., and Curzon, G. (1990) Anxiogenic-like effect of infusing 1-(3-chlorophenyl) piperazine (mcpp) into the hippocampus. Psychopharmacol. (Berl.) 100, 138–140.
Winslow, J. T., and Insel, T. R. (1990) Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation calls of rat pups. Neuropsychopharmacology 3, 51–59.
Wise, C. D., Berger, B. D., Stein, L. (1972) Benzodiazepines: anxiety-reducing activity by reduction of serotonin turnover in the brain. Science 177, 180–183.
Yamashita, S., Oishi, R., Gomita, Y. (1995) Anticonflict effects of acute and chronic treatments with buspirone and gepirone in rats. Pharmacol. Biochem. Behav. 50, 477–479.
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Gordon, J.A., Hen, R. The serotonergic system and anxiety. Neuromol Med 5, 27–40 (2004). https://doi.org/10.1385/NMM:5:1:027
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DOI: https://doi.org/10.1385/NMM:5:1:027