Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-23T22:26:42.683Z Has data issue: false hasContentIssue false
  • English
  • Français

Regional distribution of serotonergic receptors: a systems neuroscience perspective on the downstream effects of the multimodal-acting antidepressant vortioxetine on excitatory and inhibitory neurotransmission

Published online by Cambridge University Press:  07 August 2015

Alan L. Pehrson ,
Theepica Jeyarajah  and
Connie Sanchez
Alan L. Pehrson*
Affiliation:
External Sourcing and Scientific Excellence, Lundbeck Research USA, Inc., Paramus, New Jersey, USA
Theepica Jeyarajah
Affiliation:
External Sourcing and Scientific Excellence, Lundbeck Research USA, Inc., Paramus, New Jersey, USA
Connie Sanchez
Affiliation:
External Sourcing and Scientific Excellence, Lundbeck Research USA, Inc., Paramus, New Jersey, USA Clinical Medicine Department, Aarhus University, Aarhus, Denmark
*
*Address for correspondence: Dr. Alan L. Pehrson, External Sourcing and Scientific Excellence, Lundbeck Research USA, Inc., Paramus, NJ 07652, USA. (Email: apeh@lundbeck.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Previous work from this laboratory hypothesized that the multimodal antidepressant vortioxetine enhances cognitive function through a complex mechanism, using serotonergic (5-hydroxytryptamine, 5-HT) receptor actions to modulate gamma-butyric acid (GABA) and glutamate neurotransmission in key brain regions like the prefrontal cortex (PFC) and hippocampus. However, serotonergic receptors have circumscribed expression patterns, and therefore vortioxetine’s effects on GABA and glutamate neurotransmission will probably be regionally selective. In this article, we attempt to develop a conceptual framework in which the effects of 5-HT, selective serotonin reuptake inhibitors (SSRIs), and vortioxetine on GABA and glutamate neurotransmission can be understood in the PFC and striatum—2 regions with roles in cognition and substantially different 5-HT receptor expression patterns. Thus, we review the anatomy of the neuronal microcircuitry in the PFC and striatum, anatomical data on 5-HT receptor expression within these microcircuits, and electrophysiological evidence on the effects of 5-HT on the behavior of each cell type. This analysis suggests that 5-HT and SSRIs will have markedly different effects within the PFC, where they will induce mixed effects on GABA and glutamate neurotransmission, compared to the striatum, where they will enhance GABAergic interneuron activity and drive down the activity of medium spiny neurons. Vortioxetine is expected to reduce GABAergic interneuron activity in the PFC and concomitantly increase cortical pyramidal neuron firing. However in the striatum, vortioxetine is expected to increase activity at GABAergic interneurons and have mixed excitatory and inhibitory effects in medium spiny neurons. Thus the conceptual framework developed here suggests that vortioxetine will have regionally selective effects on GABA and glutamate neurotransmission.

Keywords

5-HT receptorGABAglutamateLu AA21004vortioxetine
Type
Review Articles
Information
CNS Spectrums , Volume 21 , Issue 2 , April 2016 , pp. 162 - 183
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.McIntyre, RS, Cha, DS, Soczynska, JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013; 30(6): 515–527.CrossRefGoogle ScholarPubMed
2.Jaeger, J, Berns, S, Uzelac, S, Davis-Conway, S. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006; 145(1): 39–48.CrossRefGoogle ScholarPubMed
3.Katona, C, Hansen, T, Olsen, CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012; 27(4): 215–223.CrossRefGoogle ScholarPubMed
4.McIntyre, RS, Lophaven, S, Olsen, CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014; 17(10): 1557–1567.CrossRefGoogle ScholarPubMed
5.Mahableshwarkar, AR, Zajecka, J, Jacobson, W, Chen, Y, Keefe, RS. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology. 2015; 40(8): 2025–2037.CrossRefGoogle ScholarPubMed
6.du Jardin, KG, Jensen, JB, Sanchez, C, Pehrson, AL. Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism. Eur Neuropsychopharmacol. 2014; 24(1): 160–171.CrossRefGoogle ScholarPubMed
7.Jensen, JB, du Jardin, KG, Song, D, et al. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for adirect 5-HT receptor modulation. Eur Neuropsychopharmacol. 2014; 24(1): 148–159.CrossRefGoogle Scholar
8.Mørk, A, Montezinho, LP, Miller, S, et al. Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav. 2013; 105: 41–50.CrossRefGoogle ScholarPubMed
9.Wallace, A, Pehrson, AL, Sanchez, C, Morilak, DA. Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats. Int J Neuropsychopharmacol. 2014; 17(10): 1695–1706.CrossRefGoogle ScholarPubMed
10.Li, Y, Abdourahman, A, Tamm, JA, Sanchez, C, Gulinello, M. Reversal of age-associated memory impairment by vortioxetine is associated with changes in specific gene expressions in female mice. Eur Neuropsychopharmacol. 2014; 24(Suppl 2): S370.CrossRefGoogle Scholar
11.Li, Y, Abdourahman, A, Tamm, JA, Sanchez, C, Gulinello, M. Recovery of age-related memory impairment in mice by vortioxetine is associated with activation of genes related to the neurotrophic factor signaling. Int J Neuropsychopharmacol. 2014; 17(Suppl 1): 134.Google Scholar
12.Pehrson, AL, Sanchez, C. Vortioxetine reverses social recognition memory impairments induced by acetylcholine or glutamate dysregulation in rats. Eur Neuropsychopharmacol. 2014; 24(Suppl 2): S369.CrossRefGoogle Scholar
13.Leiser, SC, Pehrson, AL, Robichaud, PJ, Sanchez, C. The multimodal antidepressant vortioxetine increases frontal cortical oscillations unlike escitalopram and duloxetine—a quantitative electroencephalographic study in the rat. Br J Pharmacol. 2014; 171(18): 4255–4272.CrossRefGoogle Scholar
14.Zohar, J, Nutt, DJ, Kupfer, DJ, et al. A proposal for an updated neuropsychopharmacological nomenclature. Eur Neuropsychopharmacol. 2014; 24(7): 1005–1014.CrossRefGoogle ScholarPubMed
15.Sanchez, C, Asin, KE, Artigas, F. Vortioxetine a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015; 145: 43–57.CrossRefGoogle ScholarPubMed
16.Pehrson, AL, Sanchez, C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr. 2014; 19(2): 121–133.CrossRefGoogle ScholarPubMed
17.Dale, E, Zhang, H, Leiser, SC, et al. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus. J Psychopharmacol. 2014; 28(10): 891–902.CrossRefGoogle ScholarPubMed
18.Riga, MS, Celada, P, Sanchez, C, Artigas, F. Role of 5-HT3 receptors in the mechanism of action of the investigational antidepressant vortioxetine. Eur Neuropsychopharmacol. 2013; 23(Suppl 2): S393–S394.CrossRefGoogle Scholar
19.Morales, M, Battenberg, E, de Lecea, L, Bloom, FE. The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus. Brain Res. 1996; 731(1–2): 199–202.CrossRefGoogle Scholar
20.Pasupathy, A, Miller, EK. Different time courses of learning-related activity in the prefrontal cortex and striatum. Nature. 2005; 433(7028): 873–876.CrossRefGoogle ScholarPubMed
21.Rosenkilde, CE, Bauer, RH, Fuster, JM. Single cell activity in ventral prefrontal cortex of behaving monkeys. Brain Res. 1981; 209(2): 375–394.CrossRefGoogle ScholarPubMed
22.Totah, NK, Kim, YB, Homayoun, H, Moghaddam, B. Anterior cingulate neurons represent errors and preparatory attention within the same behavioral sequence. J Neurosci. 2009; 29(20): 6418–6426.CrossRefGoogle ScholarPubMed
23.Clarke, HF, Dalley, JW, Crofts, HS, Robbins, TW, Roberts, AC. Cognitive inflexibility after prefrontal serotonin depletion. Science. 2004; 304(5672): 878–880.CrossRefGoogle ScholarPubMed
24.Puig, MV, Gulledge, AT. Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol. 2011; 44(3): 449–464.CrossRefGoogle ScholarPubMed
25.Kubota, Y. Untangling GABAergic wiring in the cortical microcircuit. Curr Opin Neurobiol. 2014; 26: 7–14.CrossRefGoogle ScholarPubMed
26.Adesnik, H, Scanziani, M. Lateral competition for cortical space by layer-specific horizontal circuits. Nature. 2010; 464(7292): 1155–1160.CrossRefGoogle ScholarPubMed
27.Gottlieb, JP, Keller, A. Intrinsic circuitry and physiological properties of pyramidal neurons in rat barrel cortex. Exp Brain Res. 1997; 115(1): 47–60.CrossRefGoogle ScholarPubMed
28.Dale, E, Pehrson, AL, Jeyarajah, T, et al. Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr. doi:10.1017/S1092852915000425.Google Scholar
29.Aznar, S, Qian, Z, Shah, R, Rahbek, B, Knudsen, GM. The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain. Brain Res. 2003; 959(1): 58–67.CrossRefGoogle ScholarPubMed
30.Celada, P, Puig, MV, Artigas, F. Serotonin modulation of cortical neurons and networks. Front Integr Neurosci. 2013; 7: 25.CrossRefGoogle ScholarPubMed
31.Cruz, DA, Eggan, SM, Azmitia, EC, Lewis, DA. Serotonin1A receptors at the axon initial segment of prefrontal pyramidal neurons in schizophrenia. Am J Psychiatry. 2004; 161(4): 739–742.CrossRefGoogle ScholarPubMed
32.Llado-Pelfort, L, Santana, N, Ghisi, V, Artigas, F, Celada, P. 5-HT1A receptor agonists enhance pyramidal cell firing in prefrontal cortex through a preferential action on GABA interneurons. Cereb Cortex. 2012; 22(7): 1487–1497.CrossRefGoogle ScholarPubMed
33.Bruinvels, AT, Palacios, JM, Hoyer, D. Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1993; 347(6): 569–582.CrossRefGoogle ScholarPubMed
34.Sari, Y, Lefevre, K, Bancila, M, et al. Light and electron microscopic immunocytochemical visualization of 5-HT1B receptors in the rat brain. Brain Res. 1997; 760(1–2): 281–286.CrossRefGoogle ScholarPubMed
35.Sari, Y, Miquel, MC, Brisorgueil, MJ, et al. Cellular and subcellular localization of 5-hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies. Neuroscience. 1999; 88(3): 899–915.CrossRefGoogle ScholarPubMed
36.de Groote, L, Klompmakers, AA, Olivier, B, Westenberg, HG. An evaluation of the effect of NAS-181, a new selective 5-HT(1B) receptor antagonist, on extracellular 5-HT levels in rat frontal cortex. Naunyn Schmiedebergs Arch Pharmacol. 2003; 367(2): 89–94.CrossRefGoogle ScholarPubMed
37.Tanaka, E, North, RA. Actions of 5-hydroxytryptamine on neurons of the rat cingulate cortex. J Neurophysiol. 1993; 69(5): 1749–1757.CrossRefGoogle ScholarPubMed
38.Egeland, M, Warner-Schmidt, J, Greengard, P, Svenningsson, P. Co-expression of serotonin 5-HT(1B) and 5-HT(4) receptors in p11 containing cells in cerebral cortex, hippocampus, caudate-putamen and cerebellum. Neuropharmacology. 2011; 61(3): 442–450.CrossRefGoogle Scholar
39.Peddie, CJ, Davies, HA, Colyer, FM, Stewart, MG, Rodriguez, JJ. Dendritic colocalisation of serotonin1B receptors and the glutamate NMDA receptor subunit NR1 within the hippocampal dentate gyrus: an ultrastructural study. J Chem Neuroanat. 2008; 36(1): 17–26.CrossRefGoogle ScholarPubMed
40.Peddie, CJ, Davies, HA, Colyer, FM, Stewart, MG, Rodriguez, JJ. A subpopulation of serotonin 1B receptors colocalize with the AMPA receptor subunit GluR2 in the hippocampal dentate gyrus. Neurosci Lett. 2010; 485(3): 251–255.CrossRefGoogle ScholarPubMed
41.Cornea-Hebert, V, Riad, M, Wu, C, Singh, SK, Descarries, L. Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J Comp Neurol. 1999; 409(2): 187–209.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
42.Puig, MV, Watakabe, A, Ushimaru, M, Yamamori, T, Kawaguchi, Y. Serotonin modulates fast-spiking interneuron and synchronous activity in the rat prefrontal cortex through 5-HT1A and 5-HT2A receptors. J Neurosci. 2010; 30(6): 2211–2222.CrossRefGoogle Scholar
43.Weber, ET, Andrade, R. Htr2a gene and 5-HT(2A) receptor expression in the cerebral cortex studied using genetically modified mice. Front Neurosci. 2010; 4.Google ScholarPubMed
44.Abramowski, D, Rigo, M, Duc, D, Hoyer, D, Staufenbiel, M. Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain using specific antisera. Neuropharmacology. 1995; 34(12): 1635–1645.CrossRefGoogle ScholarPubMed
45.Puig, MV, Celada, P, Diaz-Mataix, L, Artigas, F. In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents. Cereb Cortex. 2003; 13(8): 870–882.CrossRefGoogle ScholarPubMed
46.Gehlert, DR, Gackenheimer, SL, Wong, DT, Robertson, DW. Localization of 5-HT3 receptors in the rat brain using [3H]LY278584. Brain Res. 1991; 553(1): 149–154.CrossRefGoogle ScholarPubMed
47.Puig, MV, Santana, N, Celada, P, Mengod, G, Artigas, F. In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors. Cerebr Cortex. 2004; 14(12): 1365–1375.CrossRefGoogle Scholar
48.Morales, M, Battenberg, E, Bloom, FE. Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol. 1998; 402(3): 385–401.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
49.Morales, M, Bloom, FE. The 5-HT3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon. J Neurosci. 1997; 17(9): 3157–3167.CrossRefGoogle ScholarPubMed
50.Ashby, CR Jr, Minabe, Y, Edwards, E, Wang, RY. 5-HT3-like receptors in the rat medial prefrontal cortex: an electrophysiological study. Brain Res. 1991; 550(2): 181–191.CrossRefGoogle ScholarPubMed
51.Vilaro, MT, Cortes, R, Mengod, G. Serotonin 5-HT4 receptors and their mRNAs in rat and guinea pig brain: distribution and effects of neurotoxic lesions. J Comp Neurol. 2005; 484(4): 418–439.CrossRefGoogle ScholarPubMed
52.Peñas-Cazorla, R, Vilaró, MT. Serotonin 5-HT receptors and forebrain cholinergic system: receptor expression in identified cell populations. Brain Structure and Function. In press. DOI: 10.1007/s00429-014-0864-z.Google Scholar
53.Oliver, KR, Kinsey, AM, Wainwright, A, Sirinathsinghji, DJ. Localization of 5-ht(5A) receptor-like immunoreactivity in the rat brain. Brain Res. 2000; 867(1–2): 131–142.CrossRefGoogle ScholarPubMed
54.Goodfellow, NM, Bailey, CD, Lambe, EK. The native serotonin 5-HT(5A) receptor: electrophysiological characterization in rodent cortex and 5-HT(1A)-mediated compensatory plasticity in the knock-out mouse. J Neurosci. 2012; 32(17): 5804–5809.CrossRefGoogle ScholarPubMed
55.Gerard, C, Martres, MP, Lefevre, K, et al. Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res. 1997; 746(1–2): 207–219.CrossRefGoogle ScholarPubMed
56.Marazziti, D, Baroni, S, Pirone, A, et al. Serotonin receptor of type 6 (5-HT6) in human prefrontal cortex and hippocampus post-mortem: an immunohistochemical and immunofluorescence study. Neurochem Int. 2013; 62(2): 182–188.CrossRefGoogle ScholarPubMed
57.Neumaier, JF, Sexton, TJ, Yracheta, J, Diaz, AM, Brownfield, M. Localization of 5-HT(7) receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist stimulated cFos expression. J Chem Neuroanat. 2001; 21(1): 63–73.CrossRefGoogle ScholarPubMed
58.Tokarski, K, Zahorodna, A, Bobula, B, Hess, G. 5-HT7 receptors increase the excitability of rat hippocampal CA1 pyramidal neurons. Brain Res. 2003; 993(1–2): 230–234.CrossRefGoogle ScholarPubMed
59.Tokarski, K, Kusek, M, Hess, G. 5-HT7 receptors modulate GABAergic transmission in rat hippocampal CA1 area. J Physiol Pharmacol. 2011; 62(5): 535–540.Google ScholarPubMed
60.Tokarski, K, Zelek-Molik, A, Duszynska, B, et al. Acute and repeated treatment with the 5-HT7 receptor antagonist SB 269970 induces functional desensitization of 5-HT7 receptors in rat hippocampus. Pharmacol Rep. 2012; 64(2): 256–265.CrossRefGoogle ScholarPubMed
61.Seguela, P, Watkins, KC, Descarries, L. Ultrastructural relationships of serotonin axon terminals in the cerebral cortex of the adult rat. J Comp Neurol. 1989; 289(1): 129–142.CrossRefGoogle ScholarPubMed
62.Smiley, JF, Goldman-Rakic, PS. Serotonergic axons in monkey prefrontal cerebral cortex synapse predominantly on interneurons as demonstrated by serial section electron microscopy. J Comp Neurol. 1996; 367(3): 431–443.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
63.Puig, MV, Artigas, F, Celada, P. Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. Cereb Cortex. 2005; 15(1): 1–14.CrossRefGoogle ScholarPubMed
64.Amargos-Bosch, M, Bortolozzi, A, Puig, MV, et al. Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex. 2004; 14(3): 281–299.CrossRefGoogle ScholarPubMed
65.Gartside, SE, Hajos-Korcsok, E, Bagdy, E, Harsing, LG Jr, Sharp, T, Hajos, M. Neurochemical and electrophysiological studies on the functional significance of burst firing in serotonergic neurons. Neuroscience. 2000; 98(2): 295–300.CrossRefGoogle ScholarPubMed
66.Hajos, M, Gartside, SE, Varga, V, Sharp, T. In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: role of 5-HT1A receptors. Neuropharmacology. 2003; 45(1): 72–81.CrossRefGoogle Scholar
67.Zhong, P, Yan, Z. Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine. PLoS One. 2011; 6(2): e16970.CrossRefGoogle ScholarPubMed
68.Zhong, P, Yan, Z. Chronic antidepressant treatment alters serotonergic regulation of GABA transmission in prefrontal cortical pyramidal neurons. Neuroscience. 2004; 129(1): 65–73.CrossRefGoogle ScholarPubMed
69.Zhou, FM, Hablitz, JJ. Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex. J Neurophysiol. 1999; 82(6): 2989–2999.CrossRefGoogle ScholarPubMed
70.Araneda, R, Andrade, R. 5-Hydroxytryptamine2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience. 1991; 40(2): 399–412.CrossRefGoogle Scholar
71.Beique, JC, Chapin-Penick, EM, Mladenovic, L, Andrade, R. Serotonergic facilitation of synaptic activity in the developing rat prefrontal cortex. J Physiol. 2004; 556(Pt 3): 739–754.CrossRefGoogle ScholarPubMed
72.Villalobos, C, Beique, JC, Gingrich, JA, Andrade, R. Serotonergic regulation of calcium-activated potassium currents in rodent prefrontal cortex. Eur J Neurosci. 2005; 22(5): 1120–1126.CrossRefGoogle ScholarPubMed
73.Gronier, BS, Rasmussen, K. Electrophysiological effects of acute and chronic olanzapine and fluoxetine in the rat prefrontal cortex. Neurosci Lett. 2003; 349(3): 196–200.CrossRefGoogle ScholarPubMed
74.Ceci, A, Fodritto, F, Borsini, F. Repeated treatment with fluoxetine decreases the number of spontaneously active cells per track in frontal cortex. Eur J Pharmacol. 1994; 271(1): 231–234.CrossRefGoogle ScholarPubMed
75.Bétry, C, Overstreet, D, Haddjeri, N, et al. A 5-HT receptor antagonist potentiates the behavioral, neurochemical and electrophysiological actions of an SSRI antidepressant. Pharmacol Biochem Behav. 2015; 131C: 136–142.CrossRefGoogle Scholar
76.El Mansari, M, Lecours, M, Blier, P. Effects of acute and sustained administration of vortioxetine on the serotonin system in the hippocampus: electrophysiological studies in the rat brain. Psychopharmacology (Berl). 2015; 232(13): 2343–2352.CrossRefGoogle ScholarPubMed
77.Lindgren, HS, Wickens, R, Tait, DS, Brown, VJ, Dunnett, SB. Lesions of the dorsomedial striatum impair formation of attentional set in rats. Neuropharmacology. 2013; 71: 148–153.CrossRefGoogle ScholarPubMed
78.Rolls, ET. Neurophysiology and cognitive functions of the striatum. Rev Neurol (Paris). 1994; 150(8–9): 648–660.Google ScholarPubMed
79.Kawaguchi, Y, Wilson, CJ, Augood, SJ, Emson, PC. Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci. 1995; 18(12): 527–535.CrossRefGoogle ScholarPubMed
80.Wilson, CJ. GABAergic inhibition in the neostriatum. Prog Brain Res. 2007; 160: 91–110.CrossRefGoogle ScholarPubMed
81.Jaeger, D, Kita, H, Wilson, CJ. Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum. J Neurophysiol. 1994; 72(5): 2555–2558.CrossRefGoogle ScholarPubMed
82.Goldberg, JA, Reynolds, JN. Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum. Neuroscience. 2011; 198: 27–43.CrossRefGoogle ScholarPubMed
83.Luo, R, Janssen, MJ, Partridge, JG, Vicini, S. Direct and GABA-mediated indirect effects of nicotinic ACh receptor agonists on striatal neurones. J Physiol. 2013; 591(Pt 1): 203–217.CrossRefGoogle ScholarPubMed
84.Tepper, JM, Koos, T, Wilson, CJ. GABAergic microcircuits in the neostriatum. Trends Neurosci. 2004; 27(11): 662–669.CrossRefGoogle ScholarPubMed
85.Kawaguchi, Y, Wilson, CJ, Emson, PC. Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. J Neurosci. 1990; 10(10): 3421–3438.CrossRefGoogle ScholarPubMed
86.Augood, SJ, Emson, PC. Adenosine A2a receptor mRNA is expressed by enkephalin cells but not by somatostatin cells in rat striatum: a co-expression study. Brain Res Mol Brain Res. 1994; 22(1–4): 204–210.CrossRefGoogle Scholar
87.Gerfen, CR, Engber, TM, Mahan, LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990; 250(4986): 1429–1432.CrossRefGoogle ScholarPubMed
88.Gerfen, CR, Young, WS 3rd. Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain Res. 1988; 460(1): 161–167.CrossRefGoogle Scholar
89.Pollack, AE, Harrison, MB, Wooten, GF, Fink, JS. Differential localization of A2a adenosine receptor mRNA with D1 and D2 dopamine receptor mRNA in striatal output pathways following a selective lesion of striatonigral neurons. Brain Res. 1993; 631(1): 161–166.CrossRefGoogle ScholarPubMed
90.Pompeiano, M, Palacios, JM, Mengod, G. Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci. 1992; 12(2): 440–453.CrossRefGoogle ScholarPubMed
91.Ghavami, A, Stark, KL, Jareb, M, Ramboz, S, Segu, L, Hen, R. Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons. J Cell Sci. 1999; 112(Pt 6): 967–976.CrossRefGoogle ScholarPubMed
92.Boschert, U, Amara, DA, Segu, L, Hen, R. The mouse 5-hydroxytryptamine1B receptor is localized predominantly on axon terminals. Neuroscience. 1994; 58(1): 167–182.CrossRefGoogle ScholarPubMed
93.Sari, Y. Serotonin1B receptors: from protein to physiological function and behavior. Neurosci Biobehav Rev. 2004; 28(6): 565–582.CrossRefGoogle ScholarPubMed
94.Xie, Z, Lee, SP, O’Dowd, BF, George, SR. Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett. 1999; 456(1): 63–67.CrossRefGoogle ScholarPubMed
95.Ward, RP, Dorsa, DM. Colocalization of serotonin receptor subtypes 5-HT2A, 5-HT2C, and 5-HT6 with neuropeptides in rat striatum. J Comp Neurol. 1996; 370(3): 405–414.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
96.Eberle-Wang, K, Mikeladze, Z, Uryu, K, Chesselet, MF. Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats. J Comp Neurol. 1997; 384(2): 233–247.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
97.Blomeley, CP, Bracci, E. Serotonin excites fast-spiking interneurons in the striatum. Eur J Neurosci. 2009; 29(8): 1604–1614.CrossRefGoogle ScholarPubMed
98.Bonsi, P, Cuomo, D, Ding, J, et al. Endogenous serotonin excites striatal cholinergic interneurons via the activation of 5-HT 2C, 5-HT6, and 5-HT7 serotonin receptors: implications for extrapyramidal side effects of serotonin reuptake inhibitors. Neuropsychopharmacology. 2007; 32(8): 1840–1854.CrossRefGoogle ScholarPubMed
99.Vilaro, MT, Cortes, R, Gerald, C, Branchek, TA, Palacios, JM, Mengod, G. Localization of 5-HT4 receptor mRNA in rat brain by in situ hybridization histochemistry. Brain Res Mol Brain Res. 1996; 43(1–2): 356–360.CrossRefGoogle ScholarPubMed
100.Helboe, L, de Jong, I. Distribution of serotonin receptor 5-HT6 mRNA in selected neuronal populations in rat brain: a double labelling in situ hibridization study. Alzheimer’s and Dementia. 2014; 10(4 Suppl): P925–P926.Google Scholar
101.Marazziti, D, Baroni, S, Pirone, A, et al. Distribution of serotonin receptor of type 6 (5-HT(6)) in human brain post-mortem: a pharmacology, autoradiography and immunohistochemistry study. Neurochem Res. 2012; 37(5): 920–927.CrossRefGoogle Scholar
102.Varnas, K, Thomas, DR, Tupala, E, Tiihonen, J, Hall, H. Distribution of 5-HT7 receptors in the human brain: a preliminary autoradiographic study using [3H]SB-269970. Neurosci Lett. 2004; 367(3): 313–316.CrossRefGoogle Scholar
103.Rebec, GV, Curtis, SD. Reciprocal zones of excitation and inhibition in the neostriatum. Synapse. 1988; 2(6): 633–635.CrossRefGoogle ScholarPubMed
104.El Mansari, M, Radja, F, Ferron, A, Reader, TA, Molina-Holgado, E, Descarries, L. Hypersensitivity to serotonin and its agonists in serotonin-hyperinnervated neostriatum after neonatal dopamine denervation. Eur J Pharmacol. 1994; 261(1–2): 171–178.CrossRefGoogle ScholarPubMed
105.Luthman, J, Friedemann, M, Bickford, P, Olson, L, Hoffer, BJ, Gerhardt, GA. In vivo electrochemical measurements and electrophysiological studies of rat striatum following neonatal 6-hydroxydopamine treatment. Neuroscience. 1993; 52(3): 677–687.CrossRefGoogle ScholarPubMed
106.Olpe, HR, Koella, WP. The response of striatal cells upon stimulation of the dorsal and median raphe nuclei. Brain Res. 1977; 122(2): 357–360.CrossRefGoogle ScholarPubMed
107.Contreras, CM, Sanchez Estrada, G, Molina Hernandez, M, Marvan, ML. Electroconvulsive shock decreases excitatory responses to serotonin in the caudate nucleus of the rat. Prog Neuropsychopharmacol Biol Psychiatry. 1994; 18(1): 193–199.CrossRefGoogle ScholarPubMed
108.Blomeley, C, Bracci, E. Excitatory effects of serotonin on rat striatal cholinergic interneurones. J Physiol. 2005; 569(Pt 3): 715–721.CrossRefGoogle ScholarPubMed
109.Bahuguna, J, Aertsen, A, Kumar, A. Existence and control of go/no-go decision transition threshold in the striatum. PLoS Comput Biol. 2015; 11(4): e1004233.CrossRefGoogle ScholarPubMed
110.Baarendse, PJ, Vanderschuren, LJ. Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats. Psychopharmacology (Berl). 2012; 219(2): 313–326.CrossRefGoogle ScholarPubMed
111.Humpston, CS, Wood, CM, Robinson, ES. Investigating the roles of different monoamine transmitters and impulse control using the 5-choice serial reaction time task. J Psychopharmacol. 2013; 27(2): 213–221.CrossRefGoogle ScholarPubMed
112.Bang-Andersen, B, Ruhland, T, Jorgensen, M, et al. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011; 54(9): 3206–3221.CrossRefGoogle ScholarPubMed
113.Paxinos, G, Watson, C. The Rat Brain in Stereotaxic Coordinates. 4th ed. San Diego: Academic Press; 1998.Google Scholar