Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice

Abstract

Vasopressin affects behavior via its two brain receptors, the vasopressin 1a and vasopressin 1b receptors (Avpr1b). Recent work from our laboratory has shown that disruption of the Avpr1b gene reduces intermale aggression and reduces social motivation. Here, we further characterized the aggressive phenotype in Avpr1b -/- (knockout) mice. We tested maternal aggression and predatory behavior. We also analyzed the extent to which food deprivation and competition over food increases intermale aggression. We quantified defensive behavior in Avpr1b -/- mice and later tested offensive aggression in these same mice. Our results show that attack behavior toward a conspecific is consistently reduced in Avpr1b -/- mice. Predatory behavior is normal, suggesting that the deficit is not because of a global inability to detect and attack stimuli. Food deprivation, competition for food and previous experience increase aggression in both Avpr1b +/+ and -/- mice. However, in these circumstances, the level of aggression seen in knockout mice is still less than that observed in wild-type mice. Defensive avoidance behaviors, such as boxing and fleeing, are largely intact in knockout mice. Avpr1b -/- mice do not display as many 'retaliatory' attacks as the Avpr1b +/+ mice. Interestingly, when territorial aggression was measured following the defensive behavior testing, Avpr1b -/- mice typically show less initial aggressive behavior than wild-type mice, but do show a significant increase in aggression with repeated testing. These studies confirm that deficits in aggression in Avpr1b -/- mice are limited to aggressive behavior involving the attack of a conspecific. We hypothesize that Avpr1b plays an important role in the central processing that couples the detection and perception of social cues (which appears normal) with the appropriate behavioral response.

Figure 1

Aggression in Avpr1b +/+ and Avpr1b −/− mice in a competitive aggression paradigm. Ad lib = ad libitum food; Restricted = food deprived overnight before the test; No Food = no food present during aggression test; Food = food present during aggression test. Top Panel. The percentage of subjects attacking the stimulus animal in the single, three-minute test. The percentage of Avpr1b −/− mice in the AdLib/No Food group attacking was significantly lower than the other groups. There were no other group differences. (*=significantly lower than other groups, P<0.05) Center Panel. The mean attack latency (seconds ± SEM). There was a significant effect of genotype (Avpr1b +/+ mice attacked more quickly than Avpr1b −/− mice), restricted condition (restricted animals attacked faster than ad libitum-fed animals), and competition state (animals attacked faster when food was present during the test than when it was absent). There were no interactions among any of the factors. See Results for the statistics. Bottom Panel. The mean number of attack behaviors (± SEM) observed. There was a significant effect of genotype (Avpr1b +/+ mice exhibited more attack behaviors than Avpr1b −/− mice), food restriction (restricted animals showed more attack behavior than ad libitum-fed animals), and competition state (animals attacked more when food was present during the test than when food was absent). There were no interactions among any of the factors. See Results for the statistics.

Figure 2

Defensive behavior in Avpr1b +/+ and Avpr1b −/− mice. Top Panel. The mean number (±SEM) of attacks on the subjects observed in each test and in Tests 1-3 combined. The stimulus animals attacked both genotypes equally. There were no significant differences among the groups. Center Panel. The mean number of defenses per stimulus attack (± SEM) observed in each test and in Tests 1-3 combined There is no effect of genotype or test number. Bottom Panel. The percentage of Avpr1b −/− subjects showing defensive attack behavior is significantly lower than the percentage of Avpr1b +/+ mice displaying defensive attacks in Test 1 and Test 2, but not in Test 3 or Tests 1-3 combined. (* is p<0.05).

Figure 3

Offensive behavior in Avpr1b +/+ and Avpr1b −/− mice. Top Panel. The percentage of animals displaying offensive aggression. Center Panel. The number of attacks (± SEM) in test 4, 5, and 6 as well as the average number of attacks per test (± SEM) when the data are pooled across tests 4-6 (* = significantly lower than the other genotypes; p<0.05) Bottom Panel. The latency to attack (± SEM). Knockouts took significantly longer to attack than did wild-types. (* = significantly lower than Avpr1b +/+ group; p<0.05).