Acute and lasting effects of single mineralocorticoid antagonism on offensive aggressive behaviour in rats

• A single spironolactone injection affected the escalation of aggressive behaviour.
• Abolished attacks in the short-term, enhanced aggression in the long-term.
• Defeated intruders elicited attack behaviour.
• Spironolactone plus naïve intruders reduced variability in attack latency time.

Aggression is a major component of territorial behaviour. However, different mechanisms evolved to fulfil the defence function while reducing the cost derived from agonistic interactions, as a differential response to the same stimulus, depending on the outcome of past conflicts – priming, which makes the aggressive response adaptable. Aggressive behaviour is facilitated by the stress response, so, we tested the effect of a single injection of a mineralocorticoid antagonist (spironolactone) on the escalation of territorial aggression in a resident–intruder paradigm, and its modulation by social stimulus. We used naïve Wild Type Groningen – WTG – rats as residents, and naïve and previously defeated Wistar rats as intruders. The first encounter was 1 h after the injection, and then repeated in 3 consecutive days. When WTG rats were confronted with naïve Wistar rats, single injections of spironolactone completely abolished the attack behaviour in the short term while enhancing it in the long term. When we used defeated Wistar rats, the spironolactone effect was not as great. The short-term reduction in aggressive behaviour was attributable to the blockade of mineralocorticoid receptors during the first encounters, while the enhancement in aggressive behaviour in the long term was suggested to be related to the imbalance between mineralocorticoid and glucocorticoid receptors during the stress response associated to the encounters.