Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior

Pharmacology, Biochemistry, and Behavior
Craig F FerrisNeal G Simon

Abstract

Arginine vasopressin functions as a neurochemical signal in the brain to affect social behavior. There is an expanding literature from animal and human studies showing that vasopressin, through the vasopressin 1A receptor (V1A), can stimulate aggressive behavior. Using a novel monocylic beta lactam platform, a series of orally active vasopressin V1a antagonists was developed with high affinity for the human receptor. SRX251 was chosen from this series of V1a antagonists to screen for effects on serenic activity in a resident-intruder model of offensive aggression. Resident, male Syrian golden hamsters were given oral doses of SRX251 or intraperitoneal Manning compound, a selective V1a receptor antagonist with reduced brain penetrance, at doses of 0.2 microg, 20 microg, 2 mg/kg or vehicle. When tested 90-120 min later, SRX251, but not Manning compound, caused a significant dose-dependent reduction in offensive aggression toward intruders as measured by latency to bite and number of bites. The reduction in aggression persisted for over 6 h and was no longer present 12 h post treatment. SRX251 did not alter the amount of time the resident investigated the intruder, olfactory communication, general motor activity, or sexual motivat...Continue Reading

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Citations

Nov 7, 2006·Genes, Brain, and Behavior·S R WersingerW S Young
Nov 19, 2008·BMC Neuroscience·Craig F FerrisNeal G Simon
May 21, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Caroline F ZinkAndreas Meyer-Lindenberg
Jun 13, 2009·Cellular and Molecular Life Sciences : CMLS·Cristina LanniCinzia Boselli
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Apr 13, 2010·Frontiers in Neuroendocrinology·J M KoolhaasB Buwalda
Jun 10, 2009·Frontiers in Neuroendocrinology·Markus HeinrichsGregor Domes
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