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Volume 17, Number 11, Issue of June 1, 1997 pp. 4331-4340
Copyright ©1997 Society for Neuroscience

Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters

Received Oct. 11, 1996; revised Feb. 12, 1997; accepted March 21, 1997.

Craig F. Ferris1, Richard H. Melloni Jr1, Gary Koppel2, Kenneth W. Perry2, Ray W. Fuller2, and Yvon Delville1

1 Neuropsychiatric Sciences Program, Department of Psychiatry, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, and 2 Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285

Studies in several species of rodents show that arginine vasopressin (AVP) acting through a V1A receptor facilitates offensive aggression, i.e., the initiation of attacks and bites, whereas serotonin (5-HT) acting through a 5-HT1B receptor inhibits aggressive responding. One area of the CNS that seems critical for the organization of aggressive behavior is the basolateral hypothalamus, particularly the anterior hypothalamic region. The present studies examine the neuroanatomical and neurochemical interaction between AVP and 5-HT at the level of the anterior hypothalamus (AH) in the control of offensive aggression in Syrian golden hamsters. First, specific V1A and 5-HT1B binding sites in the AH are shown by in vitro receptor autoradiography. The binding for each neurotransmitter colocalizes with a dense field of immunoreactive AVP and 5-HT fibers and putative terminals. Putative 5-HT synapses on AVP neurons in the area of the AH are identified by double-staining immunocytochemistry and laser scanning confocal microscopy. These morphological data predispose a functional interaction between AVP and 5-HT at the level of the AH. When tested for offensive aggression in a resident/intruder paradigm, resident hamsters treated with fluoxetine, a selective 5-HT reuptake inhibitor, have significantly longer latencies to bite and bite fewer times than vehicle-treated controls. Conversely, AVP microinjections into the AH significantly shorten the latency to bite and increase biting attacks. The action of microinjected AVP to increase offensive aggression is blocked by the pretreatment of hamsters with fluoxetine. These data suggest that 5-HT inhibits fighting, in part, by antagonizing the aggression-promoting action of the AVP system.

Key words: fluoxetine; vasopressin; serotonin; anterior hypothalamus; offensive aggression; V1A receptor; 5-HT1B receptor; serenic; flank marking




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