Individual sensitivity to blockade of β1,2-adrenoceptors was studied by dividing rats into groups depending on the manifestation of conditioned reflex fear in a classical defensive conditioned reflex (low- and high-freezing animals) and on the level of anxiety in the elevated plus maze and dark-light box tests (highand low-anxiety animals). The effects due to local administration of the β1,2-adrenoceptor antagonist propranolol (1.25 μg/0.5 μl) and physiological saline (controls, 0.5 μl) into the basolateral amygdala were compared in the different groups of rats. Administration of propranolol into the amygdala before testing of previously acquired conditioned reflex fear led to a decrease in freezing time in response to the conditioned signal only in low-freezing animals, but not in high-freezing animals. Administration of propranolol into the amygdala accelerated extinction and degraded the productivity of retraining in high-freezing rats, having virtually no effect on low-freezing animals. In addition, administration of propranolol into the amygdala did not induce any significant changes in measures of anxiety in these tests in either high- or low-anxiety rats. A difference in the sensitivity of high- and low-freezing rats to injections of propranolol into the amygdala was seen. Amygdalar β1,2-adrenoceptors play a significant role in the acquisition and extinction of conditioned reflex fear in high-freezing rats, facilitating the appearance of prolonged freezing and resistance to extinction of the reflex.
Similar content being viewed by others
References
Abraham, P. A., Xing, G., Zhang, L., et al., “Beta1-and beta2-adrenoceptor induced synaptic facilitation in rat basolateral amygdale,” Brain Res., 1209, 65–73 (2008).
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).
Berlau, D. J. and McGaugh, J. L., “Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdale,” Neurobiol. Learn. Mem., 86, No. 2, 123–132 (2006).
Braga, M. F., Aroniadou-Anderjaska, V., Manion, S. T., et al., “Stress impairs alpha (1A) adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdale,” Neuropsychopharmacology, 29, No. 1, 45–58 (2004).
Bremner, J. D., Krystal, J. H., Southwick, S. M., and Charney, D. S., “Noradrenergic mechanisms in stress and anxiety: I. Preclinical studies,” Synapse, 23, 28–38 (1996).
Buffalari, D. M. and Grace, A. A., “Noradrenergic modulation of basolateral amygdale neuronal activity: opposing influences of alpha-2 and beta receptor activation,” J. Neurosci., 27, No. 45, 12358–12366 (2007).
Bush, D. E., Caparosa, E. M., Gekker, A., and LeDoux, J. E., “Betaadrenergic receptors in the lateral nucleus of the amygdale contribute to the acquisition but not the consolidation of auditory fear conditioning,” Front. Behav. Neuroscience, No. 4, 154, (2010).
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).
Caldji, C., Tannenbaum, B., Sharma, S., et al., “Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat,” Proc. Natl. Acad. Sci. USA, 95, No. 9, 5335–5340 (1998).
Camp, R. M. and Johnson, J. D., “Repeated stressor exposure enhances contextual fear memory in a beta-adrenergic receptor-dependent process and increases impulsivity in a non-beta receptor-dependent fashion,” Physiol. Behav., 150, 64–68 (2015).
Chou, D., Huang, C. C., and Hsu, K. S., “Brain-derived neurotrophic factor in the amygdale mediates susceptibility to fear conditioning,” Exp. Neurol., 255, 19–29 (2014).
Debiec, J. and LeDoux, J. E., “Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdale,” Neuroscience, 129, 267–272 (2004).
Debiec, J., Bush, D. E., and LeDoux, J. E., “Noradrenergic enhancement of reconsolidation in the amygdale impairs extinction of conditioned fear in rats – a possible mechanism for the persistence of traumatic memories in PTSD,” Depress. Anxiety, 28, No. 3, 186–193 (2011).
Do-Monte, F. H., Kincheski, G. C., Pavesi, E., et al., “Role of beta-adrenergic receptors in the ventromedial prefrontal cortex during contextual fear extinction in rats,” Neurobiol. Learn. Mem., 94, No. 3, 318–328 (2010).
Ehrlich, I., Humeau, Y., Grenier, F., et al., “Amygdala inhibitory circuits and the control of fear memory,” Neuron, 62, No. 6, 757–771 (2009).
Farb, C. R., Chang, W., and LeDoux, J. E., “Ultrastructural characterization of noradrenergic axons and Beta-adrenergic receptors in the lateral nucleus of the amygdale,” Front. Behav. Neurosci., No. 4, 162 (2010).
Ferreira, R. and Nobre, M. J., “Conditioned fear in low-and high-anxious rats is differentially regulated by cortical subcortical and midbrain 5-HT(1A) receptors,” Neuroscience, 268, 159–168 (2014).
Finley, J. C., O’Leary, M., Wester, D., et al., “A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress,” J. Appl. Physiol., 96, No. 6, 2231–2239 (2004).
Fiorenza, N. G., Rosa, J., Izquierdo, I., and Myskiw, J. C., “Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas,” Behav. Brain Res., 232, No. 1, 210–216 (2012).
Hassan, M., York, K. M., Li, Q., et al., “Association of beta1-adrenergic receptor genetic polymorphism with mental stress-induced myocardial ischemia in patients with coronary artery disease,” Arch. Intern. Med., 168, No. 7, 763–770 (2008).
Hatfield, T. and McGaugh, J. L., “Norepinephrine infused into the basolateral amygdale posttraining enhances retention in a spatial water maze task,” Neurobiol. Learn. Mem., 71, No. 2, 232–239 (1999).
LaLumiere, R. T. and McGaugh, L. M., “Memory enhancement induced by post-training intrabasolateral amygdale infusions of β-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdale,” Learn. Mem., 12, No. 5, 527–532 (2005).
Landgraf, R. and Wigger, A., “High vs. low anxiety-related behavior rats: An animal model of extremes in trait anxiety,” Behav. Genet., 32, 301–314 (2002).
Le Doux, J. E., Sakaguchi, A., and Reis, D. J., “Strain differences in fear between spontaneously hypertensive and normotensive rats,” Brain Res., 277, No. 1, 137–143 (1983).
LeDoux, J. E., “The amygdale,” Curr. Biol., 17, No. 20, 868–874 (2007).
Lee, H. R., Berger, S. Y., Stiedl, O., et al., “Post-training injections of catecholaminergic drugs do not modulate fear conditioning in rats and mice,” Neurosci. Lett., 303, No. 2, 123–126 (2001).
Li, R., Nishijo, H., Ono, T., et al., “Synapses on GABAergic neurons in the basolateral nucleus of the rat amygdale: double-labeling immunoelectron microscopy,” Synapse, 43, No. 1, 42–50 (2002).
Lovitz, E. S. and Thompson, L. T., “Memory-enhancing intra-basolateral amygdale clenbuterol infusion reduces post-burst afterhyperpolarizations in hippocampal CA1 pyramidal neurons following inhibitory avoidance learning,” Neurobiol. Learn. Mem., 119, 34–41 (2015).
Miranda, M. I., Ferry, B., and Ferreira, G., “Basolateral amygdale noradrenergic activity is involved in the acquisition of conditioned odor aversion in the rat,” Neurobiol. Learn. Mem, 88, No. 2, 260–263 (2007).
Miranda, M. I., LaLumiere, R. T., Buen, T. V., et al., “Blockade of noradrenergic receptors in the basolateral amygdale impairs taste memory,” Eur. J. Neurosci., 18, No. 9, 2605–2610 (2003).
Mueller, D. and Cahill, S. P., “Noradrenergic modulation of extinction learning and exposure therapy,” Behav. Brain Res., 208, No. 1, 1–11 (2010).
Myskiw, J. C., Izquierdo, I., and Furini, C. R., “Modulation of the extinction of fear learning,” Brain Res. Bull., 105, 61–69 (2014).
Pavlova, I. V. and Rysakova, M. P., “Effects of administration of a GABAA receptor agonist and 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).
Pavlova, I. V. and Rysakova, M. P., “Effects of administration of serotonin 5-HT1A ligands into the amygdala on the behavior of rats with different manifestations of conditioned reflex fear,” Zh. Vyssh. Nerv. Deyat., 66, No. 6, 710–724 (2016).
Pavlova, I. V. and Rysakova, M. P., “Manifestation of anxiety in Wistar rats on acquisition of conditioned reflex fear,” Zh. Vyssh. Nerv. Deyat., 65, No. 6, 719–735 (2015).
Pavlova, I. V., Rysakova, M. P., and Sergeeva, M. I., “Effects of blockade of D1 and D2 receptors in the basolateral amygdala on behavior in rats with high and low levels of anxiety and fear,” Zh. Vyssh. Nerv. Deyat., 65, No. 4, 471–485 (2015).
Paxinos, G. and Watson, C., The Rat brain in Stereotaxic Coordinates, Academic Press (1998).
Qu, L. L., Guo, N. N., and Li, B. M., “Beta1-and beta2-adrenoceptors in basolateral nucleus of amygdale and their roles in consolidation of fear memory in rats,” Hippocampus, 18, No. 11, 1131–1139 (2008).
Roozendaal, B., Castello, N. A., Vedana, G., et al., “Noradrenergic activation of the basolateral amygdale modulates consolidation of object recognition memory,” Neurobiol. Learn. Mem., 90, No. 3, 576–579 (2008).
Silberman, Y., Ariwodola, O. J., Chappell, A. M., et al., “Lateral paracapsular GABAergic synapses in the basolateral amygdale contribute to the anxiolytic effects of beta3 adrenoceptor activation,” J. Neuropsychopharmacology, 35, No. 9, 1886–1896 (2010).
Skelly, M. J., Chappell, A. M., Ariwodola, O. J., and Weiner, J. L., “Behavioral and neurophysiological evidence that lateral para-capsular GABAergic synapses in the basolateral amygdale contribute to the acquisition and extinction of fear learning,” Neurobiol. Learn. Mem., 127, 10–16 (2016).
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).
Uzsoki, B., Toth, M., and Hernadi, I., “Novelty response of rats determines the effect of prefrontal alpha-2 adrenoceptor modulation on anxiety,” Neurosci. Lett., 499, No. 3, 219–223 (2011).
Valizadegan, F., Oryan, S., Nasehi, M., and Zarrindast, M. R., “Interaction between morphine and noradrenergic system of basolateral amygdale on anxiety and memory in the elevated plus-maze test based on a test-retest paradigm,” Arch. Iran. Med., 16, No. 5, 281–287 (2013).
Villain, H., Benkahoul, A., Drougard, A., et al., “Effects of propranolol, a β-noradrenergic antagonist, on memory consolidation and reconsolidation in mice,” Front. Behav. Neurosci., 10, No. 49, 1–14 (2016).
Von Homeyer, P. and Schwinn, D. A., “Pharmacogenomics of β-adrenergic receptor physiology and response to β-blockade,” Anesth. Analg., 113, No. 6, 1305–1318 (2011).
Zaichenko, M. I., Markevich, V. A., and Grigor’yan, G. A., “Propranolol degrades memory reconsolidation after single and multiple combinations of a tone with pain,” Zh. Vyssh. Nerv. Deyat., 66, No. 2, 220–228 (2016).
Zaichenko, M. I., Merzhanova, G. Kh., and Bazhenova, D. A., “Effects of an agonist and an antagonist of α2-adrenoceptors on the selection of reward value in rats,” Zh. Vyssh. Nerv. Deyat., 65, No. 6, 747–755 (2015).
Zaichenko, M. I., Merzhanova, G. Kh., and Vanetsian, G. L., “Effects of administration of selective 5-HT1A receptor ligands on impulsive and self-controlled behavior in rats,” Zh. Vyssh. Nerv. Deyat., 62, No. 4, 465–474 (2012).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 68, No. 1, pp. 76–91, January–February, 2018.
Rights and permissions
About this article
Cite this article
Pavlova, I.V., Rysakova, M.P. The Role of β1,2-Adrenoceptors in the Amygdala in the Behavior of Rats with Different Levels of Freezing in Conditioned Reflex Fear. Neurosci Behav Physi 49, 659–671 (2019). https://doi.org/10.1007/s11055-019-00785-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-019-00785-1