The neurotransmitter mechanisms underlying the individual/group characteristics of behavior in animals were studied by comparing the effects of modulation of serotoninergic transmission in the amygdala in rats with different manifestations of conditioned reflex fear (high- and low-freezing rats). Administration of a 5-HT1A receptor agonist (8-OH-DPAT, 0.3 μg/0.5 μl) into the basolateral amygdala before testing of a previously acquired classical defensive reflex decreased freezing time in response to sound in low-freezing animals and weakened the signs of conditioned reflex fear in response to the signal. Administration of the receptor antagonist (WAY-100635, 0.2 μg/0.5 μl) decreased freezing time during exploration of context and in response to sound in all rats, which probably occurred as a result of increases in motor activity and the occurrence of a panic-like state. Administration of both the agonist and antagonist before extinction sessions accelerated extinction of the reflex in high-freezing rats, though the mechanisms of the effects of different ligands were different. Administration of receptor antagonist before retraining prevented acquisition of conditioned reflex freezing in all rats. 5-HT1A receptors in the amygdala play a major role not only in the manifestations and repeat acquisition, but also the extinction of conditioned reflex fear. High-freezing rats, as compared with low-freezing animals, were more sensitive to administration of 5-HT1 receptor ligands into the amygdala in relation to extinction and repeat acquisition.
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References
An, X. L., Zheng, X. G., Liang, J., and Bai, Y. J., “Corticosterone combined with intramedial prefrontal cortex infusion of SCH 23390 impairs the strong fear response in high fear-reactivity rats,” Psych. J., 2, No. 1, 1–10 (2013).
Aznar, S., Qian, Z., Shah, R., et al., “The 5-HT1A serotonin receptor is located on calbindin and parvalbumin-containing neurons in the rat brain,” Brain Res., 959, No. 1, 58–67 (2003).
Bader, L. R., Carboni, J. D., Burleson, C. A., and Cooper, M. A., “5-HT1A receptor activation reduces fear-related behavior following social defeat in Syrian hamsters,” Pharmacol. Biochem. Behav., 122, 182–190 (2014).
Barnes, N. M. and Sharp, T., “A review of central 5-HT receptors and their function,” Neuropharmacology, 38, No. 8, 1083–152 (1999).
Bauer, E. P., “Serotonin in fear conditioning processes,” Behav. Brain Res., 277, 68–77 (2015).
Blanchard, D. C. and Blanchard, R. J., “Ethoexperimental approaches to the biology of emotion,” Annu. Rev. Psychol., 39, 43–68 (1988).
Broekkamp, C. L., Berendsen, H. H., Jenck, F., and Van Delft, A. M., “Animal models for anxiety and response to serotonergic drugs,” Psychopathology, 22, No. 1, 2–12 (1989).
Bush, D. E., Sotres-Bayon, F. And LeDoux J. E., “Individual differences in fear: isolating fear reactivity and fear recovery phenotypes,” J. Trauma Stress, 20, No. 4, 413–422 (2007).
Campbell, B. M. and Merchant, K. M., “Serotonin 2C receptors within the basolateral amygdale induce acute fear-like responses in an open-field environment,” Brain Res., 993. No. 12, 1–9 (2003).
de Mello Cruz, A. P., Pinheiro, G., Alves, S. H., et al., “Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdale of rats exposed to the elevated plus-maze,” Psychopharmacology, 182, No. 3, 345–354 (2005).
Donatti, A. F. and Leite-Panissi, C. R., “GABAergic antagonist blocks the reduction of tonic immobility behavior induced by activation of 5-HT2 receptors in the basolateral nucleus of the amygdale in guinea pigs,” Brain Res. Bull., 79, No. 6, 358–364 (2009).
Ehrlich, I., Humeau, Y. Grenier, F., et al., “Amygdala inhibitory circuits and the control of fear memory,” Neuron, 62, No. 6, 757–771 (2009).
Ferreira, R. and Nobre, M. J., “Conditioned fear in low- and high-anxious rats is differentially regulated by cortical sub-cortical and midbrain 5-HT(1A) receptors,” Neuroscience, 268, 159–168 (2014).
Gonzalez, L. E., Andrews, N., and File, S. E., “5-HT1A and benzodiazepine receptors in the basolateral amygdale modulate anxiety in the social interaction test, but not in the elevated plus-maze,” Brain Res., 732, No. 1–2, 145–153 (1996).
Groenick, L., Joordens, R. J. Hijzen, T. H., et al., “Infusion of flesinoxan into the amygdale blocks the fear-potentiated startle,” Neuroreport, 11, No. 10, 2285–2288 (2000).
Guo, J. D., Hammack, S. E., Hazra, R., et al., “Bi-directional modulation of bed nucleus of stria terminalis neurons by 5-HT: molecular expression and functional properties of excitatory 5-HT receptor subtypes,” Neuroscience, 164, No. 4, 1776–1793 (2009).
Kawahara, H., Yoshida, M., Yokoo, H., et al., “Psychological stress increases serotonin release in the rat amygdale and prefrontal cortex assessed by in vivo microdialysis,” Neurosci. Lett., 162, No. 1–2, 81–84 (1993).
Lacivita, E., Leopoldo, M., Berardi, F., and Perrone, R., “5-HT1A receptor, an old target for new therapeutic agents,” Curr. Top. Med. Chem., 8, No. 12, 1024–1034 (2008).
LeDoux, J. E., “The amygdale,” Curr. Biol., 17, No. 20, 868–874 (2007).
Lehner, M., Taracha, E., Maciejak, P., et al., “Colocalisation of c-Fos and glucocorticoid receptor as well as of 5-HT(1A) and glucocorticoid receptor immunoreactivity-expressing cells in the brain structures of low and high anxiety rats,” Behav. Brain Res., 200, No. 1, 150–159 (2009).
Lehner, M., Taracha, E., Turzynska, D., et al., “The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies,” Behav. Brain Res., 192, No. 2, 203–215 (2008).
Lesch, K. P., Bengel, D., Heils, A., et al., “Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region,” Science, 274, No. 5292, 1527–1531 (1996).
Li, X. Inoue, T. Abekawa, T. Weng, S., et al., “5-HT1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT1A receptors in the hippocampus and amygdale,” Eur. J. Pharmacol., 532, No. 1–2, 74–80 (2006).
McDonald, A. J. and Mascagni, F., “Neuronal localization of 5-HT type 2A receptor immunoreactivity in the rat basolateral amygdale,” Neuroscience, 146, No. 1, 306–320 (2007).
Mo, B., Feng, N., Renner, K., and Forster, G., “Restraint stress increases serotonin release in the central nucleus of the amygdale via activation of corticotrophin-releasing factors receptors,” Brain Res. Bull., 76, No. 5, 493–498 (2008).
Morrison, K. E. and Cooper, M. A., “A role for 5-HT1A receptors in the basolateral amygdale in the development for conditioned defeat in Syrian hamsters,” Pharmacol. Biochem. Behav., 100, No. 3, 592–600 (2012).
Ogren, S. O., Eriksson, T. M., Elvander-Tottie, E., et al., “The role of 5-HT(1A) receptors in learning and memory,” Behav. Brain Res., 195, No. 1, 54–77 (2008).
Olivier, B., Pattij, T. Wood, S. J., et al., “The 5-HT(IA) receptor knockout mouse and anxiety,” Behav. Pharmacol., 12, No. 6–7, 439–450 (2001).
Pavlova, I. V., Rysakova, M. P., and Sergeeva, M. I., “Effects of blockade of D1 and D2 receptors in the basolateral amygdala on the behavior of rats with high and low levels of anxiety and fear,” Zh. Vyssh. Nerv. Deyat., 65, No. 3, 471–485 (2015).
Pavlova, I. V. and Rysakova, M. P., “Effects of administration of a GABAA receptor antagonist into the basolateral nucleus of the amygdala on the manifestation and extinction of fear in rats with different freezing durations,” Zh. Vyssh. Nerv. Deyat., 64, No. 4, 460–473 (2014).
Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press (1998).
Popova, N. K., Kulikov, A. V., Avgustinovich, D. F., and Shigantsov, S. K., “Characteristics of the serotonin system of the brain and anxiety in C57BL and CBA mice,” Zh. Vyssh. Nerv. Deyat., 46, No. 2, 348–354 (1996).
Rodgers, R. J. and Cole, J. C., “Anxiolytic-like effect of (S)-WAY 100135, a 5-HT1A receptor antagonist, in the murine elevated plus-maze test,” Eur. J. Pharmacol., 261, No. 3, 321–325 (1994).
Rodgers, R. J., Cole, J. C., and Davies, A., “Antianxiety and behavioral sup pressant actions of the novel 5-HT1A receptor agonist, flesinoxan,” Pharmacol. Biochem. Behav., 48, No. 4, 959–963 (1994).
Rysakova, M. P., Pavlova, I. V., and Broshevitskaya, N. D., “The role of serotonin (5-HT1A) receptors in the basolateral amygdala in modulating behavior in rats with different levels of anxiety and fear,” in: Neuroscience for Medicine and Psychology: 12th Int. Interdiscipl. Congr., Sudak, Crimea, Russia, MAKS Press, Moscow (2016).
Shuhama, R., Del-Ben, M., Loureiro, S. R., and Graeff, F. G., “Animal defense strategies and anxiety disorders,” Ann. Acad. Bras. Cienc., 79, No. 1, 97–109 (2007).
Skorzewska, A., Lehner, M., Wislowska-Stanek, A., et al., “Midazolam treatment before re-exposure to contextual fear reduces freezing behavior and amygdale activity differentially in high- and low-anxiety rats,” Pharmacol. Biochem. Behav., 129, 34–44 (2015).
Stiedl, O., Misane, I., Spiess, J., and Ogren, S. O, “Involvement of the 5-HT1A receptors in classical fear conditioning in C57BL/6J mice,” J. Neurosci., 20, No. 22, 8515–8527 (2000).
Strauss, C. V. A., Vicente, M. A., and Zangrossi, H. J., “Activation of 5-HT1A receptors in the rat basolateral amygdale induces both anxiolytic and antipanic-like effects,” Behav. Brain Res., 246, 103–110 (2013).
Stutzmann, G. E. and LeDoux, J. E., “GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdale: a mechanism for modulation of sensory inputs related to fear conditioning,” J. Neurosci., 19, No. 11, RC8, 1–4 (1999).
Umriukhin, A. E., Wigger, A., Singewald, N., and Landgraf, R., “Hypothalamic and hippocampal release of serotonin in rats bred for hyper- or hypo-anxiety,” Stress, 5, No. 4, 299–305 (2002).
Vertes, R. P. A., “PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat,” J. Comp. Neurol., 3123, No. 4, 643–668 (1991).
Vicente, M. A. and Zangrossi, H., “Serotonin-2C receptors in the basolateral nucleus of the amygdale mediate the anxiogenic effect of acute imipramine and fluoxetine administration,” Int. J. Neuropsychopharmacol., 15, No. 3, 389–400 (2012).
Yokoyama, M., Suzuki, T., Sato, T., et al., “Amygdalic levels of dopamine and serotonin rise upon exposure to conditioned fear stress without elevation of glutamate,” Neurosci. Lett., 379, No. 1, 37–41 (2005).
Youn, J., Misane, I., Eriksson, T. M., et al., “Bidirectional modulation of classical fear conditioning in mice by 5-HT(1A) receptor ligands with contrasting intrinsic activities,” Neuropharmacology, 57, No. 5–6, 567–576 (2009).
Zangrossi, H. J., Viana, M. B., and Graeff, F. G., “Anxiolytic effect of intra-amygdala injection of midazolam and 8-hydroxy-2-(di-n-propylamino)tetralin in the elevated T-maze,” Eur. J. Pharmacol., 369, No. 3, 267–270 (1999).
Zhang, G., Asgeirsdottir, H. N., Cohen, S. J., et al., “Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice,” Neuropharmacology, 64, 403–413 (2013).
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Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 66, No. 6, pp. 710–724, November–December, 2016.
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Pavlova, I.V., Rysakova, M.P. Effects of Administration of Serotonin 5-HT1A Receptor Ligands into the Amygdala on the Behavior of Rats with Different Manifestations of Conditioned Reflex Fear. Neurosci Behav Physi 48, 267–278 (2018). https://doi.org/10.1007/s11055-018-0560-1
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DOI: https://doi.org/10.1007/s11055-018-0560-1