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Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT1A receptor function in adult rats

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Abstract

Rationale

Traumatic events in early life are associated with an increased risk of psychiatric diseases in adulthood. 5-hydroxytryptamine (5-HT)1A receptors play a pivotal role in the 5-HTergic mechanisms associated with the etiology of stress-related disorders.

Objective

The goal of the present study was to investigate whether juvenile stress influences emotional control via postsynaptic 5-HT1A receptor in the hippocampus and amygdala using contextual fear conditioning test in adult rats.

Methods

The rats were subjected to aversive footshock (FS) during the third week of the postnatal period (3wFS group). During the postadolescent period (10–14 weeks postnatal), experiments were performed.

Results

The systemic administration of the 5-HT1A receptor agonist R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg/kg, i.p.) attenuated the freezing behavior in the non-FS group, but not in the 3wFS group. The bilateral local injection of 8-OH-DPAT (1 μg/side) into the amygdala decreased the freezing behavior in the non-FS group and the 3wFS group. However, the local injection of 8-OH-DPAT (1 μg/side) into the hippocampus decreased the freezing behavior in the non-FS group, but not in the 3wFS group. In a 5-HT1A receptor binding study, the Bmax of the 3wFS group decreased in the dorsal hippocampus, but not the amygdala in comparison with the non-FS group.

Conclusions

The juvenile stress attenuated the hippocampal postsynaptic 5-HT1A receptor function in context-dependent conditioned fear.

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References

  • Aisa B, Tordera R, Lasheras B, Del Río J, Ramírez MJ (2007) Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats. Psychoneuroendocrinology 32:256–266

    Article  PubMed  CAS  Google Scholar 

  • Akimova E, Lanzenberger R, Kasper S (2009) The serotonin-1A receptor in anxiety disorders. Biol Psychiatry 66:627–635

    Article  PubMed  CAS  Google Scholar 

  • Almada RC, Borelli KG, Albrechet-Souza L, Brandão ML (2009) Serotonergic mechanisms of the median raphe nucleus-dorsal hippocampus in conditioned fear: output circuit involves the prefrontal cortex and amygdala. Behav Brain Res 203:279–287

    Article  PubMed  CAS  Google Scholar 

  • Béïque JC, Campbell B, Perring P, Hamblin MW, Walker P, Mladenovic L, Andrade R (2004) Serotonergic regulation of membrane potential in developing rat prefrontal cortex: coordinated expression of 5-hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7 receptors. J Neurosci 24:4807–4817

    Article  PubMed  Google Scholar 

  • Chalmers DT, Kwak SP, Mansour A, Akil H, Watson SJ (1993) Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression. J Neurosci 13:914–923

    PubMed  CAS  Google Scholar 

  • Chubakov AR, Tsyganova VG, Sarkisova EF (1993) The stimulating influence of the raphe nuclei on the morphofunctional development of the hippocampus during their combined cultivation. Neurosci Behav Physiol 23:271–276

    Article  PubMed  CAS  Google Scholar 

  • Chugani DC, Muzik O, Rothermel R, Behen M, Chakraborty P, Mangner T, da Silva EA, Chugani HT (1997) Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Ann Neurol 42:666–669

    Article  PubMed  CAS  Google Scholar 

  • Commons KG, Connolley KR, Valentino RJ (2003) A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders. Neuropsychopharmacology 28:206–215

    Article  PubMed  CAS  Google Scholar 

  • Daval G, Vergé D, Becerril A, Gozlan H, Spampinato U, Hamon M (1987) Transient expression of 5-HT1A receptor binding sites in some areas of the rat CNS during postnatal development. Int J Dev Neurosci 5:171–180

    Article  PubMed  CAS  Google Scholar 

  • Dong HW, Petrovich GD, Swanson LW (2001) Topography of projections from amygdala to bed nuclei of the stria terminalis. Brain Res Brain Res Rev 38:192–246

    Article  PubMed  CAS  Google Scholar 

  • El Khoury A, Gruber SH, Mørk A, Mathé AA (2006) Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression. Prog Neuropsychopharmacol Biol Psychiatry 30:535–540

    Article  PubMed  CAS  Google Scholar 

  • Fallon JH, Ciofi P (1992) Distribution of monoamines within the amygdala. In: Aggleton JP (ed) The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction. Wiley-Liss, New York, pp 97–114

    Google Scholar 

  • Fanselow MS (1980) Conditioned and unconditional components of post-shock freezing. Pavlov J Biol Sci 15:177–182

    PubMed  CAS  Google Scholar 

  • Fanselow MS (2000) Contextual fear, gestalt memories, and the hippocampus. Behav Brain Res 110:73–81

    Article  PubMed  CAS  Google Scholar 

  • Fanselow MS, Helmstetter FJ (1988) Conditional analgesia, defensive freezing, and benzodiazepines. Behav Neurosci 102:233–243

    Article  PubMed  CAS  Google Scholar 

  • Feighner JP, Boyer WF (1989) Serotonin-1A anxiolytics: an overview. Psychopathology 22:21–26

    Article  PubMed  Google Scholar 

  • Golden RN (2004) Making advances where it matters: improving outcomes in mood and anxiety disorders. CNS Spectr 9:14–22

    PubMed  Google Scholar 

  • Handley SL, McBlane JW, Critchley MA, Njung’e K (1993) Multiple serotonin mechanisms in animal models of anxiety: environmental, emotional and cognitive factors. Behav Brain Res 58:203–210

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto S, Inoue T, Koyama T (1999) Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats. Eur J Pharmacol 378:23–30

    Article  PubMed  CAS  Google Scholar 

  • Heim C, Nemeroff CB (2001) The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 49:1023–1039

    Article  PubMed  CAS  Google Scholar 

  • Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH, Tecott LH (1998) Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc Natl Acad Sci USA 95:15049–15054

    Article  PubMed  CAS  Google Scholar 

  • Kalinichev M, Easterling KW, Plotsky PM, Holtzman SG (2002) Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats. Pharmacol Biochem Behav 73:131–140

    Article  PubMed  CAS  Google Scholar 

  • Khawaja X, Evans N, Reilly Y, Ennis C, Minchin MC (1995) Characterisation of the binding of [3H]WAY-100635, a novel 5-hydroxytryptamine1A receptor antagonist, to rat brain. J Neurochem 64:2716–2726

    Article  PubMed  CAS  Google Scholar 

  • Kia HK, Miquel MC, Brisorgueil MJ, Daval G, Riad M, El Mestikawy S (1996) Immunocytochemical localization of serotonin1A receptors in the rat central nervous system. J Comp Neurol 365:289–305

    Article  PubMed  CAS  Google Scholar 

  • Konno K, Matsumoto M, Togashi H, Yamaguchi T, Izumi T, Watanabe M, Iwanaga T, Yoshioka M (2007) Early postnatal stress affects the serotonergic function in the median raphe nuclei of adult rats. Brain Res 1172:60–66

    Article  PubMed  CAS  Google Scholar 

  • Koseki H, Matsumoto M, Togashi H, Miura Y, Fukushima K, Yoshioka M (2009) Alteration of synaptic transmission in the hippocampal-mPFC pathway during extinction trials of context-dependent fear memory in juvenile rat stress models. Synapse 63:805–813

    Article  PubMed  CAS  Google Scholar 

  • Kusserow H, Davies B, Hörtnagl H, Voigt I, Stroh T, Bert B, Deng DR, Fink H, Veh RW, Theuring F (2004) Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors. Brain Res Mol Brain Res 129:104–116

    Article  PubMed  CAS  Google Scholar 

  • LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184

    Article  PubMed  CAS  Google Scholar 

  • Leventopoulos M, Russig H, Feldon J, Pryce CR, Opacka-Juffry J (2009) Early deprivation leads to long-term reductions in motivation for reward and 5-HT1A binding and both effects are reversed by fluoxetine. Neuropharmacology 56:692–701

    Article  PubMed  CAS  Google Scholar 

  • Li X, Inoue T, Abekawa T, Weng S, Nakagawa S, Izumi T, Koyama T (2006) 5-HT1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT1A receptors in the hippocampus and amygdala. Eur J Pharmacol 532:74–80

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto M, Togashi H, Konno K, Koseki H, Hirata R, Izumi T, Yamaguchi T, Yoshioka M (2008) Early postnatal stress alters the extinction of context-dependent conditioned fear in adult rats. Pharmacol Biochem Behav 89:247–252

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki H, Izumi T, Matsumoto M, Togashi H, Yamaguchi T, Yoshida T, Watanabe M, Yoshioka M (2009) Early postnatal stress affects 5-HT1A receptor function in the medial prefrontal cortex in adult rats. Eur J Pharmacol 615:76–82

    Article  PubMed  CAS  Google Scholar 

  • McQuade R, Sharp T (1997) Functional mapping of dorsal and median raphe 5-hydroxytryptamine pathways in forebrain of the rat using microdialysis. J Neurochem 69:791–796

    Article  PubMed  CAS  Google Scholar 

  • Miquel MC, Doucet E, Boni C, SEl M, Matthiessen L, Daval G, Verge D, Hamon M (1991) Central serotonin1A receptors: respective distributions of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain. Neurochem Int 19:453–465

    Article  CAS  Google Scholar 

  • Miquel MC, Kia HK, Boni C, Doucet E, Daval G, Matthiessen L, Hamon M, Vergé D (1994) Postnatal development and localization of 5-HT1A receptor mRNA in rat forebrain and cerebellum. Brain Res Dev Brain Res 80:149–157

    Article  PubMed  CAS  Google Scholar 

  • Ohmura Y, Yamaguchi T, Izumi T, Matsumoto M, Yoshioka M (2008) Corticotropin releasing factor in the median raphe nucleus is involved in the retrieval of fear memory in rats. Eur J Pharmacol 584:357–360

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230

    Article  PubMed  CAS  Google Scholar 

  • Pryce CR, Bettschen D, Nanz-Bahr NI, Feldon J (2003) Comparison of the effects of early handling and early deprivation on conditioned stimulus, context, and spatial learning and memory in adult rats. Behav Neurosci 117:883–893

    Article  PubMed  Google Scholar 

  • Rittenhouse PA, Bakkum EA, O’Connor PA, Carnes M, Bethea CL, van de Kar LD (1992) Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear. Brain Res 580:205–214

    Article  PubMed  CAS  Google Scholar 

  • Roche M, Commons KG, Peoples A, Valentino RJ (2003) Circuitry underlying regulation of the serotonergic system by swim stress. J Neurosci 23:970–977

    PubMed  CAS  Google Scholar 

  • Schosser A, Kasper S (2009) The role of pharmacogenetics in the treatment of depression and anxiety disorders. Int Clin Psychopharmacol 24:277–288

    Article  PubMed  Google Scholar 

  • Shea A, Walsh C, Macmillan H, Steiner M (2004) Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology 30:162–178

    Article  Google Scholar 

  • Stamatakis A, Mantelas A, Papaioannou A, Pondiki S, Fameli M, Stylianopoulou F (2006) Effect of neonatal handling on serotonin 1A sub-type receptors in the rat hippocampus. Neuroscience 140:1–11

    Article  PubMed  CAS  Google Scholar 

  • Sullivan GM, Apergis J, Bush DE, Johnson LR, Hou M, Ledoux JE (2004) Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus. Neuroscience 128:7–14

    Article  PubMed  CAS  Google Scholar 

  • Vicentic A, Francis D, Moffett M, Lakatos A, Rogge G, Hubert GW, Harley J, Kuhar MJ (2006) Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain. Neuroscience 140:355–365

    Article  PubMed  CAS  Google Scholar 

  • Walker DL, Davis M (1997) Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. J Neurosci 17:9375–9383

    PubMed  CAS  Google Scholar 

  • Walker DL, Toufexis DJ, Davis M (2003) Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol 463:199–216

    Article  PubMed  CAS  Google Scholar 

  • Wright DE, Seroogy KB, Lundgren KH, Davis BM, Jennes L (1995) Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol 351:357–373

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka M, Matsumoto M, Togashi H, Saito H (1995) Effects of conditioned fear stress on 5-HT release in the rat prefrontal cortex. Pharmacol Biochem Behav 51:515–519

    Article  PubMed  CAS  Google Scholar 

  • Zhong P, Ciaranello RD (1995) Transcriptional regulation of hippocampal 5-HT1a receptors by corticosteroid hormones. Brain Res Mol Brain Res 29:23–34

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Dr. Shigeo Miyata and Dr. Katsuzi Suzuki for helpful advice. The authors also thank Dr. Kasane Higuchi and Dr. Kotaro Konno for their excellent technical support. This study was supported by Japanese Ministry of Education grants No. 0677074 (T. I.).

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Authors and Affiliations

  1. Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, 060, Japan

    Hirokazu Matsuzaki, Takeshi Izumi, Taku Yamaguchi, Takayuki Yoshida & Mitsuhiro Yoshioka

  2. Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Takahiro Horinouchi & Soichi Miwa

  3. Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Shuken Boku, Takeshi Inoue & Tsukasa Koyama

  4. Department of Pharmacological Science, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan

    Machiko Matsumoto & Hiroko Togashi

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  1. Hirokazu Matsuzaki
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  2. Takeshi Izumi
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Correspondence to Takeshi Izumi.

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Matsuzaki, H., Izumi, T., Horinouchi, T. et al. Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT1A receptor function in adult rats. Psychopharmacology 214, 329–337 (2011). https://doi.org/10.1007/s00213-010-1987-4

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  • DOI: https://doi.org/10.1007/s00213-010-1987-4

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