In male golden hamsters, offensive aggression is regulated by an interaction between arginine-vasopressin and serotonin at the level of the anterior hypothalamus. The present studies were conducted to study a neural network underlying this interaction. The connections of the anterior hypothalamus were examined by retrograde and anterograde tracing in adult male hamsters. Several limbic areas were found to contain both types of tracing suggesting reciprocal connections with the anterior hypothalamus. Their functional significance relating to the consummation of aggression was tested by comparing neuronal activity (examined through quantification of c-Fos-immunolabeling) in two groups of animals. Experimental animals were sacrificed after attacking an intruder. Control animals were sacrificed after exposure to a woodblock carrying the odor of an intruder that elicited behaviors related to offensive aggression without its consummation. An increased density of Fos-immunoreactivity was found in experimental animals within the medial amygdaloid nucleus, ventrolateral hypothalamus, bed nucleus of the stria terminalis and dorsolateral part of the midbrain central gray. These data suggest that these areas are integrated in a neural network centered on the anterior hypothalamus and involved in the consummation of offensive aggression. Finally, c-Fos-immunoreactivity was combined with labeling of serotonin and vasopressin neurons to identify sub-populations particularly associated with offensive aggression. Vasopressin neurons in the nucleus circularis and medial division of the supraoptic nucleus showed increased neuronal activity in the fighters, supporting their role in the control of offensive aggression.

1.
Adams, D.B. (1971) Defence and territorial behaviour dissociated by hypothalamic lesions in the rat. Nature, 232: 573–574.
2.
Albert, D.J., and M.L. Walsh (1984) Neural systems and the inhibitory modulation of agonistic behavior: a comparison of mammalian species. Neurosci. Behav. Rev., 8: 5–24.
3.
Albert, D.J., E.M. Dyson, and M.L. Walsh (1987) Intermale social aggression: Reinstatement in castrated rats by implants of testosterone propionate in the medial hypothalamus. Physiol. Behav., 39: 555–560.
4.
Albert, D.J., D.M. Petrovic, R.H. Jonik, and M.L. Walsh (1991) Enhanced defensiveness and increased food motivation each contribute to aggression and success in food competition by rats with medial hypothalamic lesions. Physiol. Behav., 49: 13–19.
5.
Bamshad, M., and H.E. Albers (1996) Neural circuitry controlling vasopressin-stimulated scent marking in Syrian hamsters (Mesocricetus auratus). J. Comp. Neurol., 369: 252–263.
6.
Berghorn, K.A., J.H. Bonnett, and G.E. Hoffman (1994) cFos immunoreactivity is enhanced with biotin amplification. J. Histochem. Cytochem., 42: 1635–1642.
7.
Berk, M.L., and J.A. Finkelstein (1981) Afferent projections to the preoptic area and hypothalamic regions in the rat brain. Neuroscience, 6: 1601–1624.
8.
Bermond, B., J. Mos, W. Meelis, A.M. van der Poel, and M.R. Kruk (1982) Aggression induced by stimulation of the hypothalamus: Effects of androgens. Pharmacol. Biochem. Behav., 16: 41–45.
9.
Blanchard, D.C., and R.J. Blanchard (1988) Ethoexperimental approaches to the biology of emotion. Ann. Rev. Psychol., 39: 43–68.
10.
Blanchard, R.J., and D.C. Blanchard (1977) Aggressive behavior in the rat. Behav. Biol., 21: 197–224.
11.
Brain, P.F. (1981) Differentiating types of attacks and defense in rodents. In Multidisciplinary Approaches to Aggression Research (ed. by P.F. Brain and D. Benton), Elsevier, New York, pp. 53–77.
12.
Bunnell, B.N., F.J. Sodetz Jr., and D.I. Shalloway (1970) Amygdaloid lesions and social behavior in the golden hamster. Physiol. Behav., 5: 153– 161.
13.
Cameron, A.A., I.A. Khan, K.N. Westlund, K.D. Cliffer, and W.D. Willis (1995) The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris-leucoagglutinin study. I. Ascending projections. J. Comp. Neurol., 351: 568–584.
14.
Canteras, N.S., R.B. Simerly, and L.W. Swanson (1992) Connections of the posterior nucleus of the amygdala. J. Comp. Neurol., 324: 143–179.
15.
Chang, H.T., H. Kuo, J.A. Whittaker, and N.G. Cooper (1990) Light and electron microscopic analysis of projection neurons retrogradely labeled with Fluoro-Gold: notes on the application of antibodies to Fluoro-Gold. J. Neurosci. Methods, 35: 31–37.
16.
Colpaert, F.C., and P.R. Wiepkema (1976) Effects of ventromedial hypothalamic lesions on spontaneous intraspecific aggression in male rats. Behav. Biol., 16: 117–125.
17.
Conrad, L.C.A., and D.W. Pfaff (1976) Efferents from medial basal forebrain and hypothalamus in the rat. II. An autoradiographic study of the anterior hypothalamus. J. Comp. Neurol., 169: 221–261.
18.
Coolen, L.M., and R.I. Wood (1998) Bidirectional connections of the medial amygdaloid nucleus in the Syrian hamster brain: simultaneous anterograde and retrograde tract tracing. J. Comp. Neurol., 21: 189–209.
19.
Delville, Y., and J.D. Blaustein (1993) Estrogen receptor-immunoreactive forebrain neurons project to the ventrolateral hypothalamus in female guinea pigs. J. Comp. Neurol., 334: 571–589.
20.
Delville, Y., E.T. Koh, and C.F. Ferris (1994) Sexual differences in the magnocellular vasopressinergic system in golden hamsters. Brain Res. Bull., 33: 535–540.
21.
Delville, Y., K.M. Mansour, and C.F. Ferris (1996a) Serotonin blocks vasopressin-facilitated offensive aggression: interactions within the ventrolateral hypothalamus of golden hamsters. Physiol. Behav., 59: 813–816.
22.
Delville, Y., K.M. Mansour, and C.F. Ferris (1996b) Testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus. Physiol. Behav., 60: 25–29.
23.
de Olmos, J.S., and W.R. Ingram (1972) The projection field of the stria terminalis in the rat brain. An experimental study. J. Comp. Neurol., 146: 303–334.
24.
de Olmos, J.S., G.F. Alheid, and C.A. Beltramo (1985) Amygdala. In The Rat Nervous System, Vol. I, Forebrain and Midbrain (ed. by G. Paxinos), Academic Press, San Diego, pp. 223– 334.
25.
Dragunow, M., and R. Faull (1989) The use of c-fos as a metabolic marker in neuronal pathway tracing. J. Neurosci. Methods, 29: 261–265.
26.
Ebling, F.J, E.S. Maywood, M. Mehta, D.C. Hancock, S. McNulty, J. De Bono, S.J. Bray, and M.H. Hastings (1996) FosB in the suprachiasmatic nucleus of the Syrian and Siberian hamster. Brain Res. Bull., 41: 257–268.
27.
Eclancher, F.S.M, and P. Karli (1971) Comportement d’agressions interspécifiques et comportement alimentaire du rat: effets de lésions des noyaux ventro-médians de l’hypothalamus. Brain Res., 26: 71–79.
28.
Fénelon, V.S., D.T. Theodosis, and D.A. Poulain (1994) Fos synthesis in identified magnocellular neurons varies with phenotype, stimulus, location in the hypothalamus and reproductive state. Brain Res., 662: 165–177.
29.
Ferris, C.F., and M. Potegal (1988) Vasopressin receptor blockade in the anterior hypothalamus suppresses intraspecific aggression in male golden hamsters. Physiol. Behav., 44: 235–239.
30.
Ferris, C.F., H.E. Albers, S.M. Weslowski, B.D. Goldman, and S.E. Leeman (1984) Microinjection of vasopressin into a discrete hypothalamic site triggers a complex stereotypic behavior in golden hamsters. Science, 224: 521–523.
31.
Ferris, C.F., Y. Delville, Z. Gronka, J. Luber-Narod, and T.R. Insel (1993) An iodinated vasopressin antagonist blocks flank marking and selectively labels neural binding sites in golden hamsters. Physiol. Behav., 54: 737–747.
32.
Ferris, C.F., Y. Delville, R.W. Irvin, and M. Potegal (1994) Septo-hypothalamic organization of stereotypic behavior controlled by vasopressin in golden hamsters. Physiol. Behav., 55: 755– 759.
33.
Ferris, C.F., L. Gold, G.J. De Vries, and M. Potegal (1990a) Evidence for a functional anatomical relationship between the lateral septum and the hypothalamus in the control of vasopressin dependent flank marking behavior in golden hamsters. J. Comp. Neurol., 293: 476–485.
34.
Ferris, C.F., R.W. Irvin, M. Potegal, and J.F. Axelson (1990b) Kainic acid lesion of vasopressinergic neurons in the hypothalamus disrupts flank marking behavior in golden hamsters. J. Neuroendocrinol., 2: 123–129.
35.
Ferris, C.F., R.H. Melloni, Jr., G. Koppel, K.W. Perry, R.W.Fuller, and Y. Delville (1997) Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. J. Neurosci., 17: 4331–4340.
36.
Ferris, C.F., C.G. Pilapil, D. Hayden-Hixson, R.G. Wiley, and E.T. Koh (1992) Functionally and anatomically distinct populations of vasopressinergic magnocellular neurons in the female golden hamster. J. Neuroendocrinol., 4: 193– 205.
37.
Ferris, C.F., T.L. Stolberg, and Y. Delville (1999) Serotonin regulation of aggressive behavior in male golden hamsters. Behav. Neurosci., 113: 804–815.
38.
Gerfen, C.R., and P.E. Sawchenko (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunocytochemical of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res., 290: 219–238.
39.
Gomez, D.M., and S.W. Newman (1992) Differential projections of the anterior and posterior regions of the medial amygdaloid nucleus in the Syrian hamster. J. Comp. Neurol., 317: 195–218.
40.
Halsell, C.B. (1992) Organization of parabrachial nucleus efferents to the thalamus and amygdala in the golden hamster. J. Comp. Neurol., 317: 57–78.
41.
Hammond, M.A., and F.A. Rowe (1976) Medial preoptic and anterior hypothalamic lesions: effects on aggressive behavior in female hamsters. Physiol. Behav., 17: 507–513.
42.
Hennessey, A.C., D.C. Whitman, and H.E. Albers (1992) Microinjection of arginine-vasopressin into the periacqueductal gray stimulates flank marking in Syrian hamsters (Mesocricetus auratus). Brain Res., 569: 136–140.
43.
Herbert, H., M.M. Moga, and C.B. Saper (1990) Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J. Comp. Neurol., 293: 54–580.
44.
Holets, V.R., T. Hökfelt, Å. Rökaeus, L. Terenius, and M. Goldstein (1988) Locus coeruleus neurons in the rat containing neuropeptide Y, tyrosine hydroxylase or galanin and their efferent projections to the spinal cord, cerebral cortex and hypothalamus. Neuroscience, 24: 893– 906.
45.
Irvin, R.W., P. Szot, D.M. Dorsa, M. Potegal, and C.F. Ferris (1990) Vasopressin in the septal area of the golden hamster controls scent marking and grooming. Physiol. Behav., 48: 693–699.
46.
Joppa, M.A., R.K. Rowe, and R.L. Meisel (1997) Effects of serotonin 1A or 1B receptor agonists on social aggression in male and female Syrian hamsters. Pharmacol. Biochem. Behav., 58: 349–353.
47.
Kevetter, G.A., and S.S. Winans (1981) Connections of the corticomedial amygdala in the golden hamster. I. Efferents of the ‘vomeronasal amygdala’. J. Comp. Neurol., 197: 81– 98.
48.
Kita, H., and Y. Oomura (1982) An HRP study of the afferent connections to the rat medial hypothalamic region. Brain Res. Bull., 8: 53–62.
49.
Kollack-Walker, S., and S.W. Newman (1995) Mating and agonistic behavior produce different patterns of fos immunolabeling in the male Syrian hamster brain. Neuroscience, 66: 721– 736.
50.
Kollack-Walker, S., S.J. Watson, and H. Akil (1997) Social stress in hamsters: defeat activates specific neurocircuits within the brain. J. Neurosci., 17: 8842–8855.
51.
Krettek, J.E., and J.L. Price (1978) Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat. J. Comp. Neurol., 178: 225–254.
52.
Kruk, M.R., A.M. Van der Poel, W. Meelis, J. Hermans, P.G. Mostert, J. Mos, and A.H.M. Lohman (1983) Discriminant analysis of the localization of aggression-inducing electrode placements in the hypothalamus of male rats. Brain Res., 260: 61–79.
53.
Lammers, J.H.C.M., M.R. Kruk, W. Meelis, and A.M. van der Poel (1988) Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat. Brain Res., 449: 311–327.
54.
Luiten, P.G.M., J.M. Koolhaas, S. de Boer, and S.J. Koopmans (1985) The cortico-medial amygdala in the central nervous system organization of agonistic behavior. Brain Res., 332: 283– 297.
55.
Matsuo, M., Y. Kataoka, S. Mataki, Y. Kato, and K. Oi (1996) Conflict situation increases serotonin release in rat dorsal hippocampus: in vivo study with microdialysis and Vogel test. Neurosci. Lett., 215: 197–200.
56.
Meibach, R.C., and A. Siegel (1977) Efferent connections of the septal area in the rat: an analysis utilizing retrograde and anterograde transport methods. Brain Res., 119: 1–20.
57.
Mendlin, A., F.J. Martin, L.E. Rueter, and B.L. Jacobs (1996) Neuronal release of serotonin in the cerebellum of behaving rats: an in vivo microdialysis study. J. Neurochem., 67: 617– 622.
58.
Morin, L.P., N. Goodless-Sanchez, L. Smale, and R.Y. Moore (1994) Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster. Neurosci., 61: 391–410.
59.
Olivier, B. (1977) The ventromedial hypothalamus and aggressive behavior in rats. Aggr. Behav., 3: 47–56.
60.
Paxinos, G., and C. Watson (1997) The Rat Brain in Stereotaxic Coordinates. Academic Press, San Diego.
61.
Peters, R.V., N. Aronin, and W.J. Schwartz (1994) Circadian regulation of Fos B is different from c-Fos in the rat suprachiasmatic nucleus. Mol. Brain Res., 27: 243–248.
62.
Potegal, M., and C.F. Ferris (1990) Intraspecific aggression in male hamsters is inhibited by vasopressin receptor antagonists. Aggr. Behav., 15: 311–320.
63.
Potegal, M., A. Blau, and M. Glusman (1981a) Effects of anteroventral septal lesions on intraspecific aggression in male hamsters. Physiol. Behav., 26: 407–412.
64.
Potegal, M., A. Blau, and M. Glusman (1981b) Inhibition of intraspecific aggression in male hamsters by septal stimulation. Physiol. Psychol., 9: 213–218.
65.
Potegal, M., C.F. Ferris, M. Herbert, J. Meyerhoff, and L. Skaredoff (1996a) Attack priming in female Syrian golden hamsters is associated with a c-fos-coupled process within the corticomedial amygdala. Neuroscience, 75: 869–880.
66.
Potegal, M., M. Herbert, M. DeCoster, and J.L. Meyerhoff (1996b) Brief, high-frequency stimulation of the corticomedial amygdala induces a delayed and prolonged increase of aggressiveness in male Syrian golden hamsters. Behav. Neurosci., 110: 401–412.
67.
Price, J.L., B.M. Slotnick, and M.F. Revial (1991) Olfactory projections to the hypothalamus. J. Comp. Neurol., 306: 447–461.
68.
Raisman, G. (1972) An experimental study of the projection of the amygdala to the accessory olfactory bulb and its relationship to the concept of a dual olfactory system. Exp. Brain Res., 14: 395–408.
69.
Ricciardi, K.H.N., J.C. Turcotte, G.J. De Vries, and J.D. Blaustein (1996) Efferent projections from the ovarian steroid receptor-containing area of the ventrolateral hypothalamus in female guinea pigs. J. Neuroendocrinol., 8: 673–685.
70.
Risold, P.Y., N.S. Canteras, and L.W. Swanson (1994) Organization of projections from the anterior hypothalamic nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J. Comp. Neurol., 348: 1–40.
71.
Robert, F.R., B.P. Léon-Henri, M.M. Chapleur-Chateau, M.N. Girr, and A.J. Burlet (1985) Comparison of three immunoassays in the screening and characterization of monoclonal antibodies against arginine-vasopressin. J. Immunol., 9: 205–220.
72.
Roeling, T.A.P., J.G. Veening, M.R. Kruk, J.P.W. Peters, M.E.J. Vermelis, and R. Nieuwenhuys (1994) Efferent connections of the hypothalamic ‘aggression area’ in the rat. Neuroscience, 59: 1001–1024.
73.
Rueter, L.E., and B.L. Jacobs (1996) A microdialysis examination of serotonin release in the rat forebrain induced by behavioral/environmental manipulations. Brain Res., 739: 57–69.
74.
Sakanaka, M., S. Shiasaka, K. Takatsuki, S. Inagaki, H. Takagi, E. Senba, Y. Kawai, T. Matsuzaki, and M. Tohyama (1981) Experimental immunohistochemical studies on the amygdalofugal peptidergic (substance P and somatostatin) fibers in the stria terminalis of the rat. Brain Res., 221: 231–242.
75.
Saper, C.B., and A.D. Loewy (1980) Efferent connections of the parabrachial nucleus in the rat. Brain Res., 197: 291–317.
76.
Saper, C.B., L.W. Swanson, and W.M. Cowan (1976) The efferent connections of the ventromedial nucleus of the hypothalamus of the rat. J. Comp. Neurol., 169: 409–442.
77.
Scalia, F., and S.S. Winans (1975) The differential projections of the olfactory bulb and accessory olfactory bulb in mammals. J. Comp. Neurol., 161: 31–56.
78.
Schmued, L.C., and J.H. Fallon (1986) Fluoro-Gold: a new fluorescent retrograde axonal tracer with numerous unique properties. Brain Res., 377: 147–154.
79.
Semenenko, F.M., and B.M. Lumb (1992) Projections of anterior hypothalamic neurons to the dorsal and ventral periaqueductal grey in the rat. Brain Res., 582: 237–245.
80.
Senba, E., S. Umemoto, Y. Kawai, and K. Noguchi (1994) Differential expression of fos family and jun family mRNAs in the rat hypothalamo-pituitary-adrenal axis after immobilization stress. Mol. Brain Res., 24: 283–294.
81.
Shipley, J.E., and B. Kolb (1977) Neural correlates of species-typical behavior in the Syrian golden hamster. J. Comp. Physiol. Psychol., 91: 1056– 1073.
82.
Shipley, M.T., J. Luna, and J.H. McLean (1989) Processing and analysis of neuroanatomical images. In Neuroanatomical Tract Tracing Methods 2 (ed. by L. Heimer and L. Zaborsky), Plenum Press, New York, pp. 331–390.
83.
Siegel, H.I. (1985) Aggressive behavior. In The Hamster. Reproduction and Behavior (ed. by H.I. Siegel), Plenum Press, New York, pp. 261– 286.
84.
Sodetz, F.J., and B.N. Bunnell (1970) Septal ablation and the social behavior of the golden hamsters. Physiol. Behav., 5: 79–88.
85.
Staiger, J.F., and F. Nürnberger (1991) The efferent connections of the lateral septal nucleus in the guinea pig: projections to the diencephalon and brainstem. Cell Tissue Res., 264: 391–413.
86.
Swanson, L.W. (1976) An autoradiographic study of the efferent connections of the preoptic region in the rat. J. Comp. Neurol., 167: 227– 256.
87.
Swanson, L.W., and W.M. Cowan (1979) The connections of the septal region in the rat. J. Comp. Neurol., 186: 621–656.
88.
Thellier, D., F. Moos, P. Richard, and M.E. Stoeckel (1994) Evidence for reciprocal connections between the dorsochiasmatic area and the hypothalamo neurohypophyseal system and some related extrahypothalamic structures. Brain Res. Bull., 35: 311–322.
89.
Tribollet, E., W.E. Armstrong, M. Dubois-Dauphin, and J.J. Dreifuss (1985) Extra-hypothalamic afferent inputs to the supraoptic nucleus area of the rat as determined by retrograde and anterograde tracing techniques. Neuroscience, 15: 135–148.
90.
Veening, J.G., S. Te Lie, P. Posthuma, L.M.G. Geereadts, and R. Nieuwenhuys (1987) A topographical analysis of the origin of some efferent projections from the lateral hypothalamus area in the rat. Neuroscience, 22: 537–551.
91.
Villalobos, J., and A. Ferssiwi (1987) The differential descending projections from the anterior, central and posterior regions of the lateral hypothalamic area: an autoradiographic study. Neurosci. Lett., 81: 95–99.
92.
Watson, Jr., R.E., S.J. Weigand, J.A. Clough, and G.E. Hoofman (1986) Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides, 7: 155–159.
93.
Wersinger, S.R., and M.J. Baum (1996) The temporal pattern of mating-induced immediate-early gene product immunoreactivity in LHRH and non-LHRH neurons of the estrous ferret forebrain. J. Neuroendocrinol., 8: 345–359.
94.
Winans, S.S., and F. Scalia (1970) Amygdaloid nucleus: new afferent input from the vomeronasal organ. Science, 170: 330–332.
95.
Zemlan, F.P., C.M. Leonard, L.M. Kow, and D.W. Pfaff (1978) Ascending tracts of the lateral columns of the rat spinal chord. A study using the silver impregnation and horseradish techniques. Exp. Neurol., 62: 298–334.
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