Abstract
The review summarizes the results of long-term studies on the role of the brain neurotransmitter serotonin in genetic predisposition to various types of defensive behavior. The involvement of the serotonergic brain system in the mechanisms of genetic control of both active and passive defensive responses has been established using silver foxes, Norway rats of S40 selection for low and high aggressiveness to humans, aggressive mice with genetic knockout of monoaminoxidase A, and S40 rats selected for predisposition to passive defensive response of freezing (catalepsy). The changes in the serotonergic 5-HT1A brain receptors of rats genetically predisposed to different strategies of defensive behavior were similar. However, the activity of the key enzyme of serotonin biosynthesis and the brain structures, in which serotonin metabolism was altered, significantly differed with regard to the preferred strategy. The conclusion was drawn that the 5-HT1A receptors and enzymes of serotonin metabolism in the brain are involved in implementing genetic control of defensive behavior. Expression of the 5-HT1A brain receptors was suggested to determine the levels of fear and anxiety and, consequently, the predisposition to defensive behavior, whereas the preferred strategy of defensive response (active or passive defensive) depends on genetically determined features of serotonin metabolism in the brain structures.
Similar content being viewed by others
REFERENCES
Gallup, G.G., Boren, J.L., Suares, S.D., and Wallnau, L.D., The Psychopharmacology of Tonic Immobility in Chickens, The Brain and Behavior in Fowl, Okawa, T., Ed., Tokyo: Jap. Sci., 1983, pp. 43-59.
Blanchard, R.J., Attack and Defense in Rodents as Ethoexperimental Models for the Study of Emotions, Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 1989, vol. 13, pp. S3-S14.
Lagerspetz, K.M. and Lagerspetz, K.Y., Genetic Determination of Aggressive Behavior, The Genetics of Behavior, van Abeleen, J., Ed., Amsterdam, 1974, pp. 321-346.
Popova, N.K., Genetics of Aggressive Behavior, Izv. Sib. Otd. Akad. Nauk SSSR, 1988, no. 3, pp. 120-127.
Kulikov, A.V. and Popova, N.K., Forms of Aggressive Behavior, Usp. Sovrem. Genet., 1991, pp. 131-151.
Kulikov, A.V., Kozlachkova, E.Y., Maslova, G.B., and Popova, N.K., Inheritance of Predisposition to Catalepsy in Mice, Behav. Genet., 1993, vol. 23, pp. 378-384.
Popova, N.K. and Kulikov, A.V., Genetic Analysis of Different Kinds of Aggressive Behavior, Behav. Genet., 1993, vol. 23, pp. 491-497.
Nikulina, E.M., Borodin, P.M., and Popova, N.K., Changes in Several Forms of Aggressive Behavior and Monoamine Content in the Brain in Wild Rats Selected for Reduced Aggressiveness towards Human, Zh. Vyssh. Nervn. Deyat., 1985, vol. 35,no. 4, pp. 703-708.
Popova, N.K., Naumenko, E.V., and Kolpakov, V.G., Serotonin i povedenie (Serotonin and Behavior), Novosibirsk: Nauka, 1978.
Manuck, S.B., Flory, J.D., Muldoon, M.F., and Ferrell, R.E., Central Nervous System Serotonergic Responsivity and Aggressive Disposition in Man, Physiol. Behav., 2002, vol. 77, pp. 705-709.
Moyer, K.E., Kinds of Aggression and Their Physiological Basis, Commun. Behav. Biol., 1968, vol. 2, pp. 65-87.
Belyaev, D.K., Destabilizing Selection as a Factor in Domestication, J. Hered., 1979, vol. 70, pp. 301-308.
Naumenko, E.V., Popova, N.K., Nikulina, E.M., et al., Behavior, Adrenocortical Activity, and Brain Monoamines in Norway Rats Selected for Reduced Aggressiveness towards Man, Pharmacol. Biochem. Behav., 1989, vol. 33, pp. 85-92.
Kolpakov, V.G., Barykina, N.N., and Chepkasov, I.L., Genetic Predisposition to Catatonic Behavior and Methylphenidate Sensitivity in Rats, Behav. Proc., 1981, vol. 6, pp. 269-281.
Popova, N.K., Barykina, N.N., Plyusnina, I.F., et al., Expression of the Startle Reaction in Rats Genetically Predisposed to Different Defensive Behaviors, Ros. Fiziol. Zh., 1999, vol. 85,no. 1, pp. 99-104.
Popova, N.K., Voitenko, N.N., and Trut, L.N., Changes in Brain Serotonin and 5-Hydroxyindole Acetic Acid in Silver Foxes Selected by Behavior, Dokl. Akad. Nauk SSSR, 1975, no. 223, pp. 1496-1500.
Popova, N.K., Voitenko, N.N., Kulikov, A.V., and Avgustinovich, D.F., Evidence for the Involvement of Central Serotonin in Mechanism of Domestication of Silver Foxes, Pharmacol. Biochem. Behav., 1991, vol. 40, pp. 751-756.
Kulikov, A.V., Zhanaeva, E.Yu., and Popova, N.K., Changes in Brain Tryptophan Hydroxylase Activity in Silver Foxes and Norway Rats during Behavioral Selection, Genetika (Moscow), 1989, vol. 25,no. 2, pp. 346-350.
Popova, N.K. and Zhanaeva, E.Yu., Properties, Activity Regulation, and Functional Role of Brain Tryptophan Hydroxylase, Neirokhimiya, 1988, vol. 7, pp. 274-287.
Boadle-Biber, M.C., Biosynthesis of Serotonin, Biology of Serotonergic Transmission, Chichester: Wiley, 1982, pp. 63-64.
Blanchard, D.C., Popova, N.K., Plysnina, I.F., et al., Defensive Reactions of “Wild-Type” and “Domesticated” Wild Rats to Approach and Contact by a Threat Stimulus, Aggressive Behavior, 1994, vol. 20, pp. 387-397.
Popova, N.K., Brain Serotonin in Genetically Defined Defensive Behavior, Complex Brain Functions: Conceptual Advances in Russian Neuroscience, Millar, R., Ivanitsky, A.M., and Balaban, P.M., Eds., Harwood, 1999, pp. 317-329.
Popova, N.K., Kulikov, A.V., Nikulina, E.M., et al., Serotonin Metabolism and Serotonergic Receptors in Norway Rats Selected for Low Aggressiveness to Man, Aggressive Behavior, 1991, vol. 17,no. 4, pp. 207-213.
Popova, N.K., Kulikov, A.V., Avgustinovich, D.F., et al., Effect of Domestication on the Basic Enzymes of Serotonin Metabolism and Serotonin Receptors in the Silver Foxes, Genetika (Moscow), 1997, vol. 33,no. 3, pp. 370-374.
Naumenko, E.V. and Popova, N.K., Serotonin i melatonin v regulyatsii endokrinnoi sistemy (Serotonin and Malatonin in the Regulation of the Endocrine System), Novosibirsk: Nauka, 1975.
Naumenko, E.V., Popova, N.K., and Ivanova, L.N., Neuroendocrine and Naurochemical Mechanisms of Domestication of Animals, Genetika (Moscow), 1987, vol. 23,no. 6, pp. 1011-1024.
Popova, N.K., Voitenko, N.N., Pavlova, S.I., et al., Genetics and Phenogenetics of Hormonal Characteristics of Animals: VII. Correlations between Brain Serotonin and the Hypothalamic-Pituitary-Adrenal System in Emotional Stress in Domesticated and Non-Domesticated Silver Foxes, Genetika (Moscow), 1980, vol. 26,no. 10, pp. 1865-1870.
Popova, N.K., Kulikov, A.V., Kolpakov, V.G., et al., Changes in the Brain Serotonin System in Rats Genetically Predisposed to Catalepsy, Zh. Vyssh. Nervn. Deyat., 1985, vol. 35,no. 4, pp. 742-746.
Kolpakov, V.G., Kulikov, A.V., Barykina, N.N., et al., Catalepsy and Increased Tryptophan Hydroxylase Activity in Rat Striatum, Biogenic Amines, 1985, vol. 2, pp. 131-136.
Popova, N.K. and Kulikov, A.V., On the Role of Brain Serotonin in Expression of Genetic Predisposition to Catalepsy in Animal Models, Am. J. Med. Genet. Neuropsychiatric Genet., 1995, vol. 60, pp. 214-220.
Koffer, K.B., Berney, S., and Hornykievicz, O., The Role of the Corpus Striatum in Neuroleptic and Narcotic-Induced Catalepsy, Eur. J. Pharmacol., 1978, vol. 47, pp. 81-86.
Kulikov, A.V., Kozlachkova, E.Y., and Popova, N.K., Activity of Tryptophan Hydroxylase in Brain of Hereditary Predisposed to Catalepsy Rats, Pharmacol. Biochem. Behav., 1992, vol. 43, pp. 999-1003.
Kulikov, A.V. and Voronova, I.P., The Role of Reversible phosphorylation in Genetically Determined Polymorphism for Tryptophan Hydroxylase Activity of the Brain, Byull. Eksp. Biol. Med., 1995, vol. 119, pp. 67-68.
Nutt, D.J. and Glue, P., Clinical Pharmacology of Anxiolytics and Antidepressants: A Psychopharmacological Perspective, Psychopharmacology of Anxiolytics and Antidepressants, File, S.E., Ed., New York: Pergamon, 1991, pp. 1-28.
Lesh, K.-P., The Ipsapirone/5-HT1A Receptor Challenge in Anxiety Disorders and Depression, Serotonin 1A Receptors in Depression and Anxiety, Stahl, S.M. et al., Eds., New York: Raven, 1992, pp. 135-162.
Popova, N.K., Avgustinovich, D.F., and Plyusnina, I.F., Specifics of the Binding of [3H]-8-OH-DPAT in Brain Structures of Wild Rats Selected for a Lack of Aggressiveness, Neirokhimiya, 1996, vol. 13, pp. 260-264.
Hammer, R., Hori, K., Blanchard, R., and Blanchard, D.C., Domestication Alters 5-HT1A Receptor Binding in Rat Brain, Pharmacol. Biochem. Behav., 1992, vol. 42, pp. 25-28.
Popova, N.K., Avgustinovich, D.F., Shigantsov, S.N., and Kulikov, A.V., Distribution of Serotonin 5-HT1A Receptors in the Brain of Rats Genetically Predisposed to Catalepsy, Zh. Vyssh. Nervn. Deyat., 1996, vol. 46,no. 3, pp. 578-582.
Popova, N.K., Avgustinovich, D.F., Kolpakov, V.G., and Plyusnina, I.Z., Specific [3H]8-OH-DPAT Binding in Brain Regions of Rats Genetically Predisposed to Various Defense Behavior Strategies, Pharmacol. Biochem. Behav., 1998, vol. 59, pp. 793-797.
Vishnivetskaya, G.B., Plyusnina, I.Z., and Popova, N.K., Involvement of 5-HT1A Receptors in Regulation of Various Types of Aggressive Behavior, Zh. Vyssh. Nervn. Deyat., 2001, vol. 51,no. 6, pp. 715-719.
Schreiber, R., Behavioral Pharmacology of 5-HT1A Receptor Ligands, Hamburg: Proefschrift, 1992.
Graeff, F.G., Neuroanatomy and Neurotransmitter Regulation of Defensive Behaviors and Related Emotions in Mammals, Brazil. J. Med. Biol. Res., 1994, vol. 27, pp. 811-829.
Cases, O., Seif, I., Grimsby, J., et al., Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAO-A, Science, 1995, vol. 268, pp. 1763-1766.
Brunner, H.G., Nelen, M., Breakefield, X.O., et al., Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A, Science, 1993, vol. 262, pp. 578-580.
Brunner, H.G., MAO-A Deficiency and Abnormal Behavior: Perspectives on an Association, Genetics of Criminal and Antisocial Behavior, Chichester: Wiley, 1995, pp. 155-167.
Popova, N.K., Skrinskaya, Yu.A., Amstislavskaya, T.G., et al., Behavioral Specifics of Mice Knocked-Out in Monoamine Oxidase A, Zh. Vyssh. Nervn. Deyat., 2000, vol. 50,no. 6, pp. 991-998.
Popova, N.K., Vishnivetskaya, G.B., Ivanova, E.A., et al., Altered Behavior and Alcohol Tolerance in Transgenic Mice Lacking MAO-A: A Comparison with Effects of MAO-A Inhibitor Clorgyline, Pharmacol. Biochem. Behav., 2000, vol. 67, pp. 1-9.
Popova, N.K. and Naumenko, E.V., Dominance Relations and the Pituitary-Adrenal System in Rats, Anim. Behav., 1972, vol. 20, pp. 108-110.
Popova, N.K., Gilinsky, M.A., Amstislavskaya, T.G., et al., Regional Serotonin Metabolism in the Brain of Transgenic Mice Lacking Monoamine Oxidase A, J. Neurosci. Res., 2001, vol. 66, pp. 423-427.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Popova, N.K. The Role of Brain Serotonin in the Expression of Genetically Determined Defensive Behavior. Russian Journal of Genetics 40, 624–630 (2004). https://doi.org/10.1023/B:RUGE.0000033309.92155.5a
Issue Date:
DOI: https://doi.org/10.1023/B:RUGE.0000033309.92155.5a