Limits...
Adding up the odds-Nitric oxide signaling underlies the decision to flee and post-conflict depression of aggression.

Stevenson PA, Rillich J - Sci Adv (2015)

Bottom Line: We found that crickets, which exhibit spectacular fighting behavior, flee once the sum of their opponent's aversive actions accrued during fighting exceeds a critical amount.This effect of aversive experience is mediated by the NO signaling pathway.NO's effect is manifested in losers by prolonged avoidance behavior, characteristic for social defeat in numerous species.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biology, Leipzig University, Talstraße 33, 04103 Leipzig, Germany.

ABSTRACT
Fighting is dangerous, which is why animals choose to flee once the costs outweigh the benefits, but the mechanisms underlying this decision-making process are unknown. By manipulating aggressive signaling and applying nitrergic drugs, we show that the evolutionarily conserved neuromodulator nitric oxide (NO), which has a suppressing effect on aggression in mammals, can play a decisive role. We found that crickets, which exhibit spectacular fighting behavior, flee once the sum of their opponent's aversive actions accrued during fighting exceeds a critical amount. This effect of aversive experience is mediated by the NO signaling pathway. Rather than suppressing aggressive motivation, NO increases susceptibility to aversive stimuli and with it the likelihood to flee. NO's effect is manifested in losers by prolonged avoidance behavior, characteristic for social defeat in numerous species. Intriguingly, fighting experience also induces, via NO, a brief susceptible period to aversive stimuli in winners just after victory. Our findings thus reveal a key role for NO in the mechanism underlying the decision to flee and post-conflict depression in aggressive behavior.

No MeSH data available.


Related in: MedlinePlus

The NO/cGMP pathway mediates depressed expression of aggression after social defeat.Bar charts comparing the level (left) and duration (right) of aggressive interactions between losers matched against their previous victors at different times after defeat (different animals for each time slot; circles, median; bars, IQR; n is given on left x axes). (A and B) Each pair of contestants was drug-treated before the initial (first) contest (cf. Fig. 1): (A) NO/cGMP activators (red bars: SNAP and 8Br-cGMP) and (B) inhibitors (blue bars: LNAME and ODQ). The effect of each drug is compared to its appropriate control (gray bars: Ringer-a for SNAP, Ringer-b for 8Br-cGMP, DNAME for LNAME, and DMSO for ODQ). Significant differences are indicated by asterisks (U test, *P < 0.05, **P < 0.01, ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4643817&req=5

Figure 2: The NO/cGMP pathway mediates depressed expression of aggression after social defeat.Bar charts comparing the level (left) and duration (right) of aggressive interactions between losers matched against their previous victors at different times after defeat (different animals for each time slot; circles, median; bars, IQR; n is given on left x axes). (A and B) Each pair of contestants was drug-treated before the initial (first) contest (cf. Fig. 1): (A) NO/cGMP activators (red bars: SNAP and 8Br-cGMP) and (B) inhibitors (blue bars: LNAME and ODQ). The effect of each drug is compared to its appropriate control (gray bars: Ringer-a for SNAP, Ringer-b for 8Br-cGMP, DNAME for LNAME, and DMSO for ODQ). Significant differences are indicated by asterisks (U test, *P < 0.05, **P < 0.01, ***P < 0.001).

Mentions: Treatment with nitrergic drugs before a fight (Fig. 1) also had a long-lasting influence on subsequent interactions (Fig. 2). As in many species (18), crickets that lose a contest remain submissive and retreat from any approaching male (level 1) for some 3 hours before regaining their initial aggressive state (22). Confirming earlier suggestions (17), our data show that post-conflict depression of aggression results from activation of the NO/cGMP pathway (Fig. 2A and fig. S2). In our experiments, the losers of fights between drug-treated crickets (cf. Fig. 1) were rematched against their aggressive victors at different times after defeat (Fig. 2). As opposed to controls, SNAP- or 8Br-cGMP–treated losers failed to fully regain their aggressiveness within 3 hours (U tests versus Ringer-a, SNAP: Plevel = 0.014, Pduration = 0.026, versus Ringer-b, 8Br-cGMP: Plevel = 0.037, Pduration = 0.0014; Fig. 2A), but recovered completely 12 hours later (Wilcoxon signed-rank test, SNAP first fight versus SNAP 12 hours after defeat: Plevel = 0.429, Pduration = 0.223, data not illustrated). Contrasting this, losers treated with NO/cGMP inhibitors regained their aggressiveness within only 15 min (U tests: LNAME versus DNAME and ODQ versus DMSO: Plevel and Pduration < 0.001 for both; Fig. 2B). As summarized in fig. S2, the time course of loser recovery was similar in all control groups and essentially complete within 3 hours (Ringer, DNAME, or DMSO), by which time SNAP- and 8Br-cGMP–treated crickets recovered to only 50%, whereas LNAME-, PTIO-, and ODQ-treated crickets recovered by 60% within 15 min.


Adding up the odds-Nitric oxide signaling underlies the decision to flee and post-conflict depression of aggression.

Stevenson PA, Rillich J - Sci Adv (2015)

The NO/cGMP pathway mediates depressed expression of aggression after social defeat.Bar charts comparing the level (left) and duration (right) of aggressive interactions between losers matched against their previous victors at different times after defeat (different animals for each time slot; circles, median; bars, IQR; n is given on left x axes). (A and B) Each pair of contestants was drug-treated before the initial (first) contest (cf. Fig. 1): (A) NO/cGMP activators (red bars: SNAP and 8Br-cGMP) and (B) inhibitors (blue bars: LNAME and ODQ). The effect of each drug is compared to its appropriate control (gray bars: Ringer-a for SNAP, Ringer-b for 8Br-cGMP, DNAME for LNAME, and DMSO for ODQ). Significant differences are indicated by asterisks (U test, *P < 0.05, **P < 0.01, ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643817&req=5

Figure 2: The NO/cGMP pathway mediates depressed expression of aggression after social defeat.Bar charts comparing the level (left) and duration (right) of aggressive interactions between losers matched against their previous victors at different times after defeat (different animals for each time slot; circles, median; bars, IQR; n is given on left x axes). (A and B) Each pair of contestants was drug-treated before the initial (first) contest (cf. Fig. 1): (A) NO/cGMP activators (red bars: SNAP and 8Br-cGMP) and (B) inhibitors (blue bars: LNAME and ODQ). The effect of each drug is compared to its appropriate control (gray bars: Ringer-a for SNAP, Ringer-b for 8Br-cGMP, DNAME for LNAME, and DMSO for ODQ). Significant differences are indicated by asterisks (U test, *P < 0.05, **P < 0.01, ***P < 0.001).
Mentions: Treatment with nitrergic drugs before a fight (Fig. 1) also had a long-lasting influence on subsequent interactions (Fig. 2). As in many species (18), crickets that lose a contest remain submissive and retreat from any approaching male (level 1) for some 3 hours before regaining their initial aggressive state (22). Confirming earlier suggestions (17), our data show that post-conflict depression of aggression results from activation of the NO/cGMP pathway (Fig. 2A and fig. S2). In our experiments, the losers of fights between drug-treated crickets (cf. Fig. 1) were rematched against their aggressive victors at different times after defeat (Fig. 2). As opposed to controls, SNAP- or 8Br-cGMP–treated losers failed to fully regain their aggressiveness within 3 hours (U tests versus Ringer-a, SNAP: Plevel = 0.014, Pduration = 0.026, versus Ringer-b, 8Br-cGMP: Plevel = 0.037, Pduration = 0.0014; Fig. 2A), but recovered completely 12 hours later (Wilcoxon signed-rank test, SNAP first fight versus SNAP 12 hours after defeat: Plevel = 0.429, Pduration = 0.223, data not illustrated). Contrasting this, losers treated with NO/cGMP inhibitors regained their aggressiveness within only 15 min (U tests: LNAME versus DNAME and ODQ versus DMSO: Plevel and Pduration < 0.001 for both; Fig. 2B). As summarized in fig. S2, the time course of loser recovery was similar in all control groups and essentially complete within 3 hours (Ringer, DNAME, or DMSO), by which time SNAP- and 8Br-cGMP–treated crickets recovered to only 50%, whereas LNAME-, PTIO-, and ODQ-treated crickets recovered by 60% within 15 min.

Bottom Line: We found that crickets, which exhibit spectacular fighting behavior, flee once the sum of their opponent's aversive actions accrued during fighting exceeds a critical amount.This effect of aversive experience is mediated by the NO signaling pathway.NO's effect is manifested in losers by prolonged avoidance behavior, characteristic for social defeat in numerous species.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biology, Leipzig University, Talstraße 33, 04103 Leipzig, Germany.

ABSTRACT
Fighting is dangerous, which is why animals choose to flee once the costs outweigh the benefits, but the mechanisms underlying this decision-making process are unknown. By manipulating aggressive signaling and applying nitrergic drugs, we show that the evolutionarily conserved neuromodulator nitric oxide (NO), which has a suppressing effect on aggression in mammals, can play a decisive role. We found that crickets, which exhibit spectacular fighting behavior, flee once the sum of their opponent's aversive actions accrued during fighting exceeds a critical amount. This effect of aversive experience is mediated by the NO signaling pathway. Rather than suppressing aggressive motivation, NO increases susceptibility to aversive stimuli and with it the likelihood to flee. NO's effect is manifested in losers by prolonged avoidance behavior, characteristic for social defeat in numerous species. Intriguingly, fighting experience also induces, via NO, a brief susceptible period to aversive stimuli in winners just after victory. Our findings thus reveal a key role for NO in the mechanism underlying the decision to flee and post-conflict depression in aggressive behavior.

No MeSH data available.


Related in: MedlinePlus