, Volume 222, Issue 1, pp 117–128

Infralimbic and dorsal raphé microinjection of the 5-HT1B receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice

  • S. Faccidomo
  • I. M. H. Quadros
  • A. Takahashi
  • E. W. Fish
  • K. A. Miczek
Original Investigation



Aggressive behavior and impaired impulse control have been associated with dysregulations in the serotonergic system and with impaired functioning of the prefrontal cortex. 5-HT1B receptors have been shown to specifically modulate several types of offensive aggression.


This study aims to characterize the relative importance of two populations of 5-HT1B receptors in the dorsal raphé nucleus (DRN) and infralimbic cortex (ILC) in the modulation of aggressive behavior.


Male CFW mice were conditioned on a fixed-ratio 5 schedule of reinforcement to self-administer a 6% (w/v) alcohol solution. Mice repeatedly engaged in 5-min aggressive confrontations until aggressive behavior stabilized. Next, a cannula was implanted into either the DRN or the ILC. After recovery, mice were tested for aggression after self-administration of either 1.0 g/kg alcohol or water prior to a microinjection of the 5-HT1B agonist, CP-93,129 (0–1.0 μg/infusion).


In both the DRN and ILC, CP-93,129 reduced aggressive behaviors after both water and alcohol self-administration. Intra-raphé CP-93,129 dose-dependently reduced both aggressive and locomotor behaviors. However, the anti-aggressive effects of intra-cortical CP-93,129 were behaviorally specific.


These findings highlight the importance of the serotonergic system in the modulation of aggression and suggest that the behaviorally specific effects of 5-HT1B receptor agonists are regionally selective. 5-HT1B receptors in a medial subregion of the prefrontal cortex, the ILC, appear to be critically involved in the attenuation of species-typical levels of aggression.


Microinjection Social behavior Prefrontal cortex Infralimbic cortex Aggressive behavior Serotonin Dorsal raphé 5-HT 


  1. Adell A, Celada P, Artigas F (2001) The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. J Neurochem 79:172–182PubMedCrossRefGoogle Scholar
  2. Ahlenius S, Larsson K (1998) Evidence for an involvement of 5-HT1B receptors in the inhibition of male rat ejaculatory behavior produced by 5-HTP. Psychopharmacol (Berl) 137:374–382CrossRefGoogle Scholar
  3. Bannai M, Fish EW, Faccidomo S, Miczek KA (2007) Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice. Psychopharmacol (Berl) 193:295–304CrossRefGoogle Scholar
  4. Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152PubMedCrossRefGoogle Scholar
  5. Best M, Williams JM, Coccaro EF (2002) Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder. Proc Natl Acad Sci U S A 99:8448–8453PubMedCrossRefGoogle Scholar
  6. Bouwknecht JA, Hijzen TH, van der Gugten J, Maes RA, Hen R, Olivier B (2001) Absence of 5-HT(1B) receptors is associated with impaired impulse control in male 5-HT(1B) knockout mice. Biol Psychiatry 49:557–568PubMedCrossRefGoogle Scholar
  7. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF (1979) Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Res 1:131–139PubMedCrossRefGoogle Scholar
  8. Bruinvels AT, Palacios JM, Hoyer D (1993) Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch Pharmacol 347:569–582PubMedCrossRefGoogle Scholar
  9. Bruinvels AT, Landwehrmeyer B, Gustafson EL, Durkin MM, Mengod G, Branchek TA, Hoyer D, Palacios JM (1994) Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology 33:367–386PubMedCrossRefGoogle Scholar
  10. Caramaschi D, de Boer SF, de Vries H, Koolhaas JM (2008) Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry. Behav Brain Res 189:263–272PubMedCrossRefGoogle Scholar
  11. Centenaro LA, Vieira K, Zimmermann N, Miczek KA, Lucion AB, de Almeida RM (2008) Social instigation and aggressive behavior in mice: role of 5-HT1A and 5-HT1B receptors in the prefrontal cortex. Psychopharmacol (Berl) 201:237–248CrossRefGoogle Scholar
  12. Chiavegatto S, Quadros IM, Ambar G, Miczek KA (2010) Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice. Genes Brain Behav 9:110–119PubMedCrossRefGoogle Scholar
  13. Clark MS, Neumaier JF (2001) The 5-HT1B receptor: behavioral implications. Psychopharmacol Bull 35:170–185PubMedGoogle Scholar
  14. Clark MS, Sexton TJ, McClain M, Root D, Kohen R, Neumaier JF (2002) Overexpression of 5-HT1B receptor in dorsal raphe nucleus using Herpes Simplex Virus gene transfer increases anxiety behavior after inescapable stress. J Neurosci 22:4550–4562PubMedGoogle Scholar
  15. Clark MS, Vincow ES, Sexton TJ, Neumaier JF (2004) Increased expression of 5-HT1B receptor in dorsal raphe nucleus decreases fear-potentiated startle in a stress dependent manner. Brain Res 1007:86–97PubMedCrossRefGoogle Scholar
  16. Cloninger CR (1987) Neurogenetic adaptive mechanisms in alcoholism. Science 236:410–416PubMedCrossRefGoogle Scholar
  17. da Veiga CP, Miczek KA, Lucion AB, de Almeida RM (2011) Social instigation and aggression in postpartum female rats: role of 5-Ht1A and 5-Ht1B receptors in the dorsal raphe nucleus and prefrontal cortex. Psychopharmacol (Berl) 213:475–487CrossRefGoogle Scholar
  18. Davidson RJ, Jackson DC, Kalin NH (2000) Emotion, plasticity, context, and regulation: perspectives from affective neuroscience. Psychol Bull 126:890–909PubMedCrossRefGoogle Scholar
  19. De Almeida RM, Lucion AB (1997) 8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats. Psychopharmacol (Berl) 134:392–400CrossRefGoogle Scholar
  20. de Almeida RM, Nikulina EM, Faccidomo S, Fish EW, Miczek KA (2001) Zolmitriptan—a 5-HT1B/D agonist, alcohol, and aggression in mice. Psychopharmacol (Berl) 157:131–141CrossRefGoogle Scholar
  21. De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (2006) 5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice. Psychopharmacol (Berl) 185:441–450CrossRefGoogle Scholar
  22. Evrard A, Laporte AM, Chastanet M, Hen R, Hamon M, Adrien J (1999) 5-HT1A and 5-HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5-HT1B knock-out mice. Eur J Neurosci 11:3823–3831PubMedCrossRefGoogle Scholar
  23. Faccidomo S, Bannai M, Miczek KA (2008) Escalated aggression after alcohol drinking in male mice: dorsal raphe and prefrontal cortex serotonin and 5-HT(1B) receptors. Neuropsychopharmacology 33:2888–2899PubMedCrossRefGoogle Scholar
  24. Fairbanks LA, Melega WP, Jorgensen MJ, Kaplan JR, McGuire MT (2001) Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys. Neuropsychopharmacology 24:370–378PubMedCrossRefGoogle Scholar
  25. Fehr C, Grintschuk N, Szegedi A, Anghelescu I, Klawe C, Singer P, Hiemke C, Dahmen N (2000) The HTR1B 861 G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy. Psychiatry Res 97:1–10PubMedCrossRefGoogle Scholar
  26. Ferrari PF, Palanza P, Parmigiani S, de Almeida RM, Miczek KA (2005) Serotonin and aggressive behavior in rodents and nonhuman primates: predispositions and plasticity. Eur J Pharmacol 526:259–273PubMedCrossRefGoogle Scholar
  27. Fineberg NA, Potenza MN, Chamberlain SR, Berlin HA, Menzies L, Bechara A, Sahakian BJ, Robbins TW, Bullmore ET, Hollander E (2010) Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology 35:591–604PubMedCrossRefGoogle Scholar
  28. Fish EW, Faccidomo S, Miczek KA (1999) Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253. Psychopharmacol (Berl) 146:391–399CrossRefGoogle Scholar
  29. Fish EW, McKenzie-Quirk SD, Bannai M, Miczek KA (2008) 5-HT(1B) receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running. Psychopharmacol (Berl) 197:145–156CrossRefGoogle Scholar
  30. Frankle WG, Lombardo I, New AS, Goodman M, Talbot PS, Huang Y, Hwang DR, Slifstein M, Curry S, Abi-Dargham A, Laruelle M, Siever LJ (2005) Brain serotonin transporter distribution in subjects with impulsive aggressivity: a positron emission study with [11C]McN 5652. Am J Psychiatry 162:915–923PubMedCrossRefGoogle Scholar
  31. Franklin KBJ, Paxinos G (2001) The mouse brain in sterotaxic coordinates, 2nd edn. Academic, New YorkGoogle Scholar
  32. Furay AR, Neumaier JF, Mullenix AT, Kaiyala KK, Sandygren NK, Hoplight BJ (2011) Overexpression of 5-HT(1B) mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption. Alcohol 45:19–32PubMedCrossRefGoogle Scholar
  33. Giacalone E, Tansella M, Valzelli L, Garattini S (1968) Brain serotonin metabolism in isolated aggressive mice. Biochem Pharmacol 17:1315–1327PubMedCrossRefGoogle Scholar
  34. Giancola PR (2000) Executive functioning: a conceptual framework for alcohol-related aggression. Exp Clin Psychopharmacol 8:576–597PubMedCrossRefGoogle Scholar
  35. Golembiowska K, Dziubina A (2002) Inhibition of amino acid release by 5-HT1B receptor agonist in the rat prefrontal cortex. Pol J Pharmacol 54:625–631PubMedGoogle Scholar
  36. Gowin JL, Swann AC, Moeller FG, Lane SD (2010) Zolmitriptan and human aggression: interaction with alcohol. Psychopharmacol (Berl) 210:521–531CrossRefGoogle Scholar
  37. Grant E, Macintosh JH (1963) A comparison of the social postures of some common laboratory rodents. Behaviour 21:246–295CrossRefGoogle Scholar
  38. Halasz J, Toth M, Kallo I, Liposits Z, Haller J (2006) The activation of prefrontal cortical neurons in aggression—a double labeling study. Behav Brain Res 175:166–175PubMedCrossRefGoogle Scholar
  39. Haller J, Toth M, Halasz J, De Boer SF (2006) Patterns of violent aggression-induced brain c-fos expression in male mice selected for aggressiveness. Physiol Behav 88:173–182PubMedCrossRefGoogle Scholar
  40. Higley JD, Linnoila M (1997) A nonhuman primate model of excessive alcohol intake. Personality and neurobiological parallels of type I- and type II-like alcoholism. Recent Dev Alcohol 13:191–219PubMedCrossRefGoogle Scholar
  41. Higley JD, Suomi SJ, Linnoila M (1996a) A nonhuman primate model of type II alcoholism? Part 2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Alcohol Clin Exp Res 20:643–650PubMedCrossRefGoogle Scholar
  42. Higley JD, Suomi SJ, Linnoila M (1996b) A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. Alcohol Clin Exp Res 20:629–642PubMedCrossRefGoogle Scholar
  43. Holmes A, Murphy DL, Crawley JN (2002) Reduced aggression in mice lacking the serotonin transporter. Psychopharmacol (Berl) 161:160–167CrossRefGoogle Scholar
  44. Hoplight BJ, Sandygren NA, Neumaier JF (2006) Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption. Alcohol 38:73–79PubMedCrossRefGoogle Scholar
  45. Hoyer D, Engel G, Kalkman HO (1985) Characterization of the 5-HT1B recognition site in rat brain: binding studies with (-)[125I]iodocyanopindolol. Eur J Pharmacol 118:1–12PubMedCrossRefGoogle Scholar
  46. Kable JW, Glimcher PW (2007) The neural correlates of subjective value during intertemporal choice. Nat Neurosci 10:1625–1633PubMedCrossRefGoogle Scholar
  47. Koe BK, Lebel LA, Fox CB, Macor JE (1992a) Binding and uptake studies with [H-3] Cp-93,129, a radiolabeled selective 5-Ht1B receptor ligand. Drug Dev Res 25:67–74CrossRefGoogle Scholar
  48. Koe BK, Nielsen JA, Macor JE, Heym J (1992b) Biochemical and behavioral-studies of the 5-Ht(1B) receptor agonist, Cp-94,253. Drug Dev Res 26:241–250CrossRefGoogle Scholar
  49. Kollack-Walker S, Newman SW (1995) Mating and agonistic behavior produce different patterns of Fos immunolabeling in the male Syrian hamster brain. Neuroscience 66:721–736PubMedCrossRefGoogle Scholar
  50. Lappalainen J, Long JC, Eggert M, Ozaki N, Robin RW, Brown GL, Naukkarinen H, Virkkunen M, Linnoila M, Goldman D (1998) Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch Gen Psychiatry 55:989–994PubMedCrossRefGoogle Scholar
  51. Lee MD, Simansky KJ (1997) CP-94, 253: a selective serotonin1B (5-HT1B) agonist that promotes satiety. Psychopharmacol (Berl) 131:264–270CrossRefGoogle Scholar
  52. Lin D, Boyle MP, Dollar P, Lee H, Lein ES, Perona P, Anderson DJ (2011) Functional identification of an aggression locus in the mouse hypothalamus. Nature 470:221–226PubMedCrossRefGoogle Scholar
  53. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK (1983) Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci 33:2609–2614PubMedCrossRefGoogle Scholar
  54. Lister RG, Hilakivi LA (1988) The effects of novelty, isolation, light and ethanol on the social behavior of mice. Psychopharmacol (Berl) 96:181–187CrossRefGoogle Scholar
  55. Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J, Suomi SJ, Linnoila M (1994) Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry 151:1485–1491PubMedGoogle Scholar
  56. Miczek KA, de Almeida RM (2001) Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT1B agonist anpirtoline. Psychopharmacol (Berl) 157:421–429CrossRefGoogle Scholar
  57. Miczek KA, O’Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Psychopharmacol (Berl) 57:47–55CrossRefGoogle Scholar
  58. Miczek KA, O’Donnell JM (1980) Alcohol and chlordiazepoxide increase suppressed aggression in mice. Psychopharmacol (Berl) 69:39–44CrossRefGoogle Scholar
  59. Miczek KA, Weerts EM, Tornatzky W, DeBold JF, Vatne TM (1992) Alcohol and “bursts” of aggressive behavior: ethological analysis of individual differences in rats. Psychopharmacol (Berl) 107:551–563CrossRefGoogle Scholar
  60. Miczek KA, Weerts EM, DeBold JF (1993) Alcohol, benzodiazepine-GABAA receptor complex and aggression: ethological analysis of individual differences in rodents and primates. J Stud Alcohol Suppl 11:170–179PubMedGoogle Scholar
  61. Miczek KA, Barros HM, Sakoda L, Weerts EM (1998) Alcohol and heightened aggression in individual mice. Alcohol Clin Exp Res 22:1698–1705PubMedCrossRefGoogle Scholar
  62. Moret C, Briley M (2000) The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy. Eur J Pharmacol 404:1–12PubMedCrossRefGoogle Scholar
  63. Mos J, Olivier B, Poth M, Van Oorschot R, Van Aken H (1993) The effects of dorsal raphe administration of eltoprazine, TFMPP and 8-OH-DPAT on resident intruder aggression in the rat. Eur J Pharmacol 238:411–415PubMedCrossRefGoogle Scholar
  64. National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, New YorkGoogle Scholar
  65. New AS, Gelernter J, Goodman M, Mitropoulou V, Koenigsberg H, Silverman J, Siever LJ (2001) Suicide, impulsive aggression, and HTR1B genotype. Biol Psychiatry 50:62–65PubMedCrossRefGoogle Scholar
  66. O’Hearn E, Molliver ME (1984) Organization of raphe-cortical projections in rat: a quantitative retrograde study. Brain Res Bull 13:709–726PubMedCrossRefGoogle Scholar
  67. Olivier B, van Oorschot R (2005) 5-HT1B receptors and aggression: a review. Eur J Pharmacol 526:207–217PubMedCrossRefGoogle Scholar
  68. Parsons LH, Weiss F, Koob GF (1998) Serotonin1B receptor stimulation enhances cocaine reinforcement. J Neurosci 18:10078–10089PubMedGoogle Scholar
  69. Raine A, Buchsbaum MS, Stanley J, Lottenberg S, Abel L, Stoddard J (1994) Selective reductions in prefrontal glucose metabolism in murderers. Biol Psychiatry 36:365–373PubMedCrossRefGoogle Scholar
  70. Reif A, Rosler M, Freitag CM, Schneider M, Eujen A, Kissling C, Wenzler D, Jacob CP, Retz-Junginger P, Thome J, Lesch KP, Retz W (2007) Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 32:2375–2383PubMedCrossRefGoogle Scholar
  71. Samson HH (1986) Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats. Alcohol Clin Exp Res 10:436–442PubMedCrossRefGoogle Scholar
  72. Sari Y, Miquel MC, Brisorgueil MJ, Ruiz G, Doucet E, Hamon M, Verge D (1999) Cellular and subcellular localization of 5-hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies. Neuroscience 88:899–915PubMedCrossRefGoogle Scholar
  73. Sijbesma H, Schipper J, de Kloet ER, Mos J, van Aken H, Olivier B (1991) Postsynaptic 5-HT1 receptors and offensive aggression in rats: a combined behavioural and autoradiographic study with eltoprazine. Pharmacol Biochem Behav 38:447–458PubMedCrossRefGoogle Scholar
  74. Sinha R, Cloninger CR, Parsian A (2003) Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism. Am J Med Genet B Neuropsychiatr Genet 121B:83–88PubMedCrossRefGoogle Scholar
  75. Sprouse JS (1991) Inhibition of dorsal raphe cell firing by MDL 73005EF, a novel 5-HT1A receptor ligand. Eur J Pharmacol 201:163–169PubMedCrossRefGoogle Scholar
  76. Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9PubMedCrossRefGoogle Scholar
  77. Sprouse JS, Aghajanian GK (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology 27:707–715PubMedCrossRefGoogle Scholar
  78. Sripada CS, Gonzalez R, Phan KL, Liberzon I (2010) The neural correlates of intertemporal decision-making: contributions of subjective value, stimulus type, and trait impulsivity. Hum Brain Mapp 32:1637–1648PubMedCrossRefGoogle Scholar
  79. Stern L, Zohar J, Cohen R, Sasson Y (1998) Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan. Eur Neuropsychopharmacol 8:325–328PubMedCrossRefGoogle Scholar
  80. Takahashi A, Kwa C, Debold JF, Miczek KA (2010a) GABA(A) receptors in the dorsal raphe nucleus of mice: escalation of aggression after alcohol consumption. Psychopharmacol (Berl) 211:467–477CrossRefGoogle Scholar
  81. Takahashi A, Shimamoto A, Boyson CO, DeBold JF, Miczek KA (2010b) GABA(B) receptor modulation of serotonin neurons in the dorsal raphe nucleus and escalation of aggression in mice. J Neurosci 30:11771–11780PubMedCrossRefGoogle Scholar
  82. Takahashi A, Quadros IM, de Almeida RM, Miczek KA (2011) Brain serotonin receptors and transporters: initiation vs. termination of escalated aggression. Psychopharmacol (Berl) 213:183–212CrossRefGoogle Scholar
  83. Van der Vegt BJ, Lieuwes N, Cremers TI, deBoer SF, Koolhaas JM (2003) Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats. Horm Behav 44:199–208PubMedCrossRefGoogle Scholar
  84. van Erp AM, Miczek KA (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. J Neurosci 20:9320–9325PubMedGoogle Scholar
  85. Veening JG, Coolen LM, de Jong TR, Joosten HW, de Boer SF, Koolhaas JM, Olivier B (2005) Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies. Eur J Pharmacol 526:226–239PubMedCrossRefGoogle Scholar
  86. Verge D, Daval G, Patey A, Gozlan H, el Mestikawy S, Hamon M (1985) Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol 113:463–464PubMedCrossRefGoogle Scholar
  87. Virkkunen M, Linnoila M (1993) Brain serotonin, type II alcoholism and impulsive violence. J Stud Alcohol Suppl 11:163–169PubMedGoogle Scholar
  88. Virkkunen M, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M (1994) CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 51:20–27PubMedCrossRefGoogle Scholar
  89. Virkkunen M, Eggert M, Rawlings R, Linnoila M (1996) A prospective follow-up study of alcoholic violent offenders and fire setters. Arch Gen Psychiatry 53:523–529PubMedCrossRefGoogle Scholar
  90. Volkow ND, Wang GJ, Hitzemann R, Fowler JS, Overall JE, Burr G, Wolf AP (1994) Recovery of brain glucose metabolism in detoxified alcoholics. Am J Psychiatry 151:178–183PubMedGoogle Scholar
  91. Weerts EM, Tornatzky W, Miczek KA (1993) Prevention of the pro-aggressive effects of alcohol in rats and squirrel monkeys by benzodiazepine receptor antagonists. Psychopharmacol (Berl) 111:144–152CrossRefGoogle Scholar
  92. Winstanley CA, Theobald DE, Dalley JW, Cardinal RN, Robbins TW (2006) Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice. Cereb Cortex 16:106–114PubMedCrossRefGoogle Scholar
  93. Yang Y, Raine A (2009) Prefrontal structural and functional brain imaging findings in antisocial, violent, and psychopathic individuals: a meta-analysis. Psychiatry Res 174:81–88PubMedCrossRefGoogle Scholar
  94. Zhuang X, Gross C, Santarelli L, Compan V, Trillat AC, Hen R (1999) Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors. Neuropsychopharmacology 21:52S–60SPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • S. Faccidomo
    • 1
    • 2
  • I. M. H. Quadros
    • 1
  • A. Takahashi
    • 1
    • 3
  • E. W. Fish
    • 1
    • 4
  • K. A. Miczek
    • 1
    • 5
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.Bowles Center for Alcohol StudiesUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Mouse Genomics Resource LaboratoryNational Institute of GeneticsMishimaJapan
  4. 4.Department of NeurologyUniversity of North Carolina at Chapel HillChapel HillUSA
  5. 5.Departments of Psychiatry, Pharmacology and Experimental Therapeutics, and NeuroscienceTufts UniversityBostonUSA

Personalised recommendations