Anterior hypothalamic dopamine D2 receptors modulate adolescent anabolic/androgenic steroid-induced offensive aggression in the Syrian hamster

In the Syrian hamster, treatment with anabolic/androgenic steroids (AAS) throughout adolescence increases dopamine and D2 receptor expression in the anterior hypothalamus (AH), a brain region implicated in the control of aggression. D2 receptor antagonists have reduced aggression in various species and animal models. However, these studies used systemic administration of drugs and reported concomitant changes in mobility. These data complicate the question of whether pharmacology targeting D2 receptors is specific to aggression or whether these drugs exert their antiaggressive effects through nonspecific mechanisms. To resolve this discrepancy, the current studies investigate whether administration of the D2 receptor antagonist eticlopride (0.01–10.0 μg in a final volume of 0.5 μl) into the AH modulates AAS-induced aggression. Antagonism of AH D2 receptors effectively suppressed AAS-induced aggression beginning at the 0.1 μg dose, with higher doses producing a floor effect, when compared with AAS-treated animals injected with saline into the AH. Importantly, these reductions in aggressive responding occurred in the absence of changes in locomotor behavior. Our findings identify a neuroanatomical locus where D2 receptor antagonism suppresses adolescent AAS-induced aggression in the absence of alterations to general mobility.

[1]  R. Melloni,et al.  Adolescent exposure to anabolic/androgenic steroids and the neurobiology of offensive aggression: A hypothalamic neural model based on findings in pubertal Syrian hamsters , 2010, Hormones and Behavior.

[2]  J. Schwartzer,et al.  Interactions between the dopaminergic and GABAergic neural systems in the lateral anterior hypothalamus of aggressive AAS-treated hamsters , 2009, Behavioural Brain Research.

[3]  P. Sachdev,et al.  Akathisia and second-generation antipsychotic drugs , 2009, Current opinion in psychiatry.

[4]  J. Schwartzer,et al.  Alterations in the anterior hypothalamic dopamine system in aggressive adolescent AAS-treated hamsters , 2009, Hormones and Behavior.

[5]  H. Schiöth,et al.  The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors , 2008, Brain Research.

[6]  M. Nader,et al.  A Review of the Discovery, Pharmacological Characterization, and Behavioral Effects of the Dopamine D2‐Like Receptor Antagonist Eticlopride , 2008, CNS neuroscience & therapeutics.

[7]  T. Dinan,et al.  Prolactin and dopamine: What is the connection? A Review Article , 2008, Journal of psychopharmacology.

[8]  C. Kennedy,et al.  The rewarding effect of aggression is reduced by nucleus accumbens dopamine receptor antagonism in mice , 2008, Psychopharmacology.

[9]  H. Dobson,et al.  gamma-amino butyric acid control of arginine vasopressin release from the ewe hypothalamus in vitro: sensitivity to oestradiol. , 2007, Reproduction in domestic animals = Zuchthygiene.

[10]  C. Pedraza,et al.  Anti-aggressive effects of GHB in OF.1 strain mice: Involvement of dopamine D2 receptors , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[11]  Elyssa B. Margolis,et al.  The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? , 2006, The Journal of physiology.

[12]  W. Muir,et al.  Effects of raclopride on aggression and stress in diversely selected chicken lines , 2006, Behavioural Brain Research.

[13]  P. Brundin,et al.  Induction of dopaminergic neurons from growth factor expanded neural stem/progenitor cell cultures derived from human first trimester forebrain , 2006, Brain Research Bulletin.

[14]  R. Melloni,et al.  Serotonin-1A receptor activity and expression modulate adolescent anabolic/androgenic steroid-induced aggression in hamsters , 2006, Pharmacology Biochemistry and Behavior.

[15]  A. Bari,et al.  D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement , 2005, Neuroscience.

[16]  Stefano Parmigiani,et al.  Escalated aggressive behavior: dopamine, serotonin and GABA. , 2005, European journal of pharmacology.

[17]  R. Melloni,et al.  Serotonin-1B receptor activity and expression modulate the aggression-stimulating effects of adolescent anabolic steroid exposure in hamsters. , 2005, Behavioral neuroscience.

[18]  J. Goodson The vertebrate social behavior network: Evolutionary themes and variations , 2005, Hormones and Behavior.

[19]  A. Kiss,et al.  Fos expression variances in mouse hypothalamus upon physical and osmotic stimuli: Co-staining with vasopressin, oxytocin, and tyrosine hydroxylase , 2005, Brain Research Bulletin.

[20]  R. Melloni,et al.  Glutamic acid decarboxylase (GAD65) immunoreactivity in brains of aggressive, adolescent anabolic steroid-treated hamsters , 2003, Hormones and Behavior.

[21]  A. Kindlundh,et al.  Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D1- and D2-receptors in the rat brain , 2003, Brain Research.

[22]  Y. Delville,et al.  Repeated exposure to social stress alters the development of agonistic behavior in male golden hamsters , 2003, Hormones and Behavior.

[23]  K. Miczek,et al.  ß Federation of European Neuroscience Societies Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats , 2022 .

[24]  R. Melloni,et al.  Serotonin modulates offensive attack in adolescent anabolic steroid-treated hamsters , 2002, Pharmacology Biochemistry and Behavior.

[25]  R. Melloni,et al.  Repeated Anabolic-Androgenic Steroid Treatment during Adolescence Increases Vasopressin V1A Receptor Binding in Syrian Hamsters: Correlation with Offensive Aggression , 2002, Hormones and Behavior.

[26]  Y. Delville,et al.  Chronic social stress during puberty enhances tyrosine hydroxylase immunoreactivity within the limbic system in golden hamsters , 2002, Brain Research.

[27]  A. Beilina,et al.  Increase of tyrosine hydroxylase and dopamine transporter mRNA levels in ventral tegmental area of male mice under influence of repeated aggression experience. , 2001, Brain research. Molecular brain research.

[28]  F. Drago,et al.  The "low-dose" concept and the paradoxical effects of prolactin on grooming and sexual behavior. , 2000, European journal of pharmacology.

[29]  D. Connor,et al.  Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters , 2000, Psychoneuroendocrinology.

[30]  B. Moghaddam,et al.  Tactile stimulation activates dopamine release in the lateral septum , 2000, Brain Research.

[31]  J. Magnusson,et al.  The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum , 2000, Brain Research.

[32]  J. Navarro,et al.  Acute and subchronic effects of pimozide on isolation-induced aggression in male mice , 2000, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[33]  L. Stinus,et al.  Effects of SCH 23390, Raclopride, and Haloperidol on Morphine Withdrawal-Induced Aggression in Male Mice , 1999, Pharmacology Biochemistry and Behavior.

[34]  S. Newman The Medial Extended Amygdala in Male Reproductive Behavior A Node in the Mammalian Social Behavior Network , 1999, Annals of the New York Academy of Sciences.

[35]  M. Rodríguez-Arias,et al.  Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice , 1998, European Neuropsychopharmacology.

[36]  J. Navarro,et al.  Acute and Subchronic Effects of Tiapride on Isolation-Induced Aggression in Male Mice , 1997, Pharmacology Biochemistry and Behavior.

[37]  C. Ferris,et al.  Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters , 1997, The Journal of Neuroscience.

[38]  C. Ferris,et al.  Anabolic-Androgenic Steroid Exposure During Adolescence and Aggressive Behavior in Golden Hamsters , 1997, Physiology & Behavior.

[39]  S. Kuhlman,et al.  D2 dopamine receptor involvement in the rough-and-tumble play behavior of juvenile rats. , 1996, Behavioral neuroscience.

[40]  R. Wood,et al.  Androgen and estrogen receptors coexist within individual neurons in the brain of the Syrian hamster. , 1995, Neuroendocrinology.

[41]  D. Lorrain,et al.  Extracellular dopamine in the medial preoptic area: implications for sexual motivation and hormonal control of copulation , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  D. Giuliani,et al.  Behavioural assessment in rats of the antipsychotic potential of the potent dopamine D2 receptor antagonist, (-)eticlopride. , 1995, Pharmacological research.

[43]  C. Ferris,et al.  Vasopressin and serotonin interactions in the control of agonistic behavior , 1994, Psychoneuroendocrinology.

[44]  D. Katz,et al.  Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes. , 1994, Archives of general psychiatry.

[45]  J. Miñarro,et al.  Behavioral profile of raclopride in agonistic encounters between male mice , 1994, Pharmacology Biochemistry and Behavior.

[46]  J. Navarro,et al.  Antiaggressive and motor effects of haloperidol show different temporal patterns in the development of tolerance , 1993, Physiology & Behavior.

[47]  P. Brain,et al.  Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice. , 1993, General pharmacology.

[48]  E. Nikulina,et al.  Role of dopamine receptors in the regulation of aggression in mice; relationship to genotype , 1992, Neuroscience and Behavioral Physiology.

[49]  P. Brain,et al.  Clozapine: Strong antiaggressive effects with minimal motor impairment , 1992, Physiology & Behavior.

[50]  A. Siegel,et al.  D2 dopamine receptor-mediated mechanisms in the medial preoptic-anterior hypothalamus regulate affective defense behavior in the cat , 1991, Brain Research.

[51]  C. Gerfen,et al.  Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[52]  M. Potegal,et al.  Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters , 1988, Physiology & Behavior.

[53]  M. Hadfield,et al.  Isolation-induced fighting in mice and regional brain monoamine utilization , 1988, Behavioural Brain Research.

[54]  D. Katz,et al.  Anabolic-Androgenic Steroid Use Among 1,010 College Men. , 1988, The Physician and sportsmedicine.

[55]  G. Siann Advances in the Study of Aggression, R.J. Blanchard, D.C. Blanchard (Eds.). Academic Press, Orlando, Florida (1986), viii , 1988 .

[56]  S. Pellis,et al.  Play-fighting in the Syrian golden hamster Mesocricetus auratus Waterhouse, and its relationship to serious fighting during postweaning development. , 1988, Developmental psychobiology.

[57]  M. Le Moal,et al.  Differential reactivity of dopaminergic neurons in the nucleus accumbens in response to different behavioral situations. An in vivo voltammetric study in free moving rats , 1986, Brain Research.

[58]  L. Spear,et al.  Periadolescence: age-dependent behavior and psychopharmacological responsivity in rats. , 1983, Developmental psychobiology.

[59]  C. J. Lerwill,et al.  The agonistic behaviour of the golden hamster Mesocricetus auratus (waterhouse) , 1971 .

[60]  G. Rebec,et al.  The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats , 2004, Psychopharmacology.

[61]  A. Randrup,et al.  Specific antagonism by dopamine inhibitors of items of amphetamine induced aggressive behaviour , 2004, Psychopharmacologia.

[62]  L. P. Morin,et al.  stereotaxic atlas of the golden hamster brain , 2001 .

[63]  J. Navarro,et al.  An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. , 1999, Methods and findings in experimental and clinical pharmacology.

[64]  D. Sibley,et al.  Molecular neurobiology of dopaminergic receptors. , 1993, International review of neurobiology.

[65]  P. Seeman,et al.  Dopamine D1 and D2 receptor selectivities of agonists and antagonists. , 1988, Advances in experimental medicine and biology.

[66]  D. Grandy,et al.  Cloning and expression of a rat D2 dopamine receptor cDNA , 1988, Nature.

[67]  D. Pfaff,et al.  Steroid hormones and aggressive behavior: approaches to the study of hormone-sensitive brain mechanisms for behavior. , 1974, Research publications - Association for Research in Nervous and Mental Disease.