title: Mineralocorticoid receptor blockade during a rat's first violent encounter inhibits its subsequent propensity for violence.
abstract: In individuals naïve to serious conflict in an unfamiliar environment, violence has long-lasting effects on subsequent aggressive behavior. This effect of the stressful experience of a first violent conflict occurs in victims as well as offenders. The authors study in the male rat as offender the role of a rapid corticosterone signal mediated by brain mineralocorticoid receptors (MR) in adjusting the threshold of aggressive responses. For this purpose, the authors have applied electrical stimulation of the brain's aggression circuit via the hypothalamic attack area or HAA. Using this paradigm, they found that in inexperienced rats, retesting of the animals on subsequent days facilitated aggression. Hypothalamic attack thresholds decreased to about 50% of their initial level. However, blocking the MR once with the mineralocorticoid antagonist spironolactone, during the very first evoked attacks, permanently prevented attack facilitation in subsequent conflicts in that same environment. The MR-mediated effect blocked by the antagonist occurred within an hour following the start of the first aggression tests only. A later MR blockade was not effective. These findings suggest that the corticosterone stress response during a very first serious conflict initializes an enhanced propensity for violent aggression through the brain MR.
authors.affiliation: Medical Pharmacology, Leiden Academic Center for Drug Research (LACDR), Gorlaeus Lab, Einsteinweg 55, Leiden 2333 CC, the Netherlands. info@mennokruk.nl
authors.forename: Menno R
authors.initials: MR
authors.lastname: Kruk
authors.forename: Jozsef
authors.initials: J
authors.lastname: Haller
authors.forename: Wout
authors.initials: W
authors.lastname: Meelis
authors.forename: E Ronald
authors.initials: ER
authors.lastname: de Kloet
mesh_terms: D000374:Aggression / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone