An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior.

Abstract

Decreased oxytocin levels in the amygdalas of rat dams following chronic gestational cocaine exposure have been correlated with heightened maternal aggressive behavior. In this experiment, drug-naive dams were implanted with bilateral cannulas into the central nucleus of the amygdala (CNA) or control area and infused with 1,000 or 500 ng of an oxytocin antagonist (OTA) or buffer, 4 hr before testing. Behavior was compared among dams infused with OTA into target areas just outside the CNA and cocaine-treated dams (infused with buffer). Dams infused with 1,000 ng OTA attacked intruders significantly more often than buffer-infused dams. OTA did not affect other behaviors, suggesting that disruption of oxytocin activity in the CNA may be sufficient to selectively alter maternal aggressive behavior.Maternal aggressive behavior is a robust type of offensive aggressive behavior found in lactating female rats (Erskine, Barfield, & Goldman, 1978;Flannelly & Flannelly, 1987;Olivier & Mos, 1992). It has been characterized by a set of postures, threats, and attacks used by mothers to protect their young from intruders that may attack or kill them (Numan, 1994). Although specific components may vary across species, virtually all mammals systematically protect their offspring (Nelson, 1995). Therefore, maternal aggressive behavior is generally considered to be adaptive, helping to ensure that pups survive what would otherwise be the most vulnerable period of their lives.However, following chronic gestational cocaine administration, rat dams can become highly aggressive toward an intruder (relative to saline-treated dams), leaving their young unprotected and vulnerable or allowing, and in some cases causing, offspring to be injured during the interaction (Johns, Faggin, Noonan, Li, Zimmerman, & Pedersen, 1995;Johns, Noonan, Zimmerman, Li, & Pedersen, 1994, 1997. This heightened level of maternal aggressive behavior is evidenced by a decreased latency to attack intruders and an increased frequency of attacks (Heyser, Molina, & Spear, 1992;Johns et al., 1994Johns et al., , 1995 (Johns, Noonan, et al., 1997). Chronic cocaineinduced increases in maternal aggressive behavior have been reported to occur during the midlactational period, on post-partum days (PPDs) 6 and 10 (Heyser et al., 1992;Johns et al., , 1995Johns, Noonan, et al., 1997), but not during the early postpartum period (Lubin, Meter, Walker, & Johns, 2001) when cocaine-induced disruptions of maternal behavior have been reported . Potentiated aggressive behavior during the midlactational period has been consistently correlated with decreased levels of the neuropeptide oxytocin (OT), specifically in the amygdala (Johns et al., 1995;Johns, Noonan, et al., 1998), a structure implicated in both normal maternal behavior (Fleming, Vaccarino, & Luebke, 1980), and pup cannibalism and viciousness (Grossman, Grossman, & Walsh, 1975).A growing body of literature reveals that pregnant rats given cocaine daily throughout gestation have decreased amygdala OT levels and incre...

Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy

“…In animal models, gestational cocaine exposure leads to deficits in oxytocinergic activity, and to diminished maternal but increased aggressive behaviors, effects similar to those seen in dams treated centrally with an oxytocin antagonist rather than cocaine (Johns, Lubin et al, 1997;Johns, Noonan et al, 1997Lubin, Elliott et al, 2003). In the present investigation, mothers with gestational cocaine exposure reported more hostility and depressed mood, a trend towards more life stress over the past month, and less social support and sense of mastery and control in their lives.…”

“…Mother rats that have higher rates of maternal behavior (licking and grooming their pups) than other dams also have markedly higher oxytocin receptor density in the amygdala (Champagne & Meaney, 2001). Significantly lower oxytocin levels are found in the amygdala during the postpartum period when rat mothers gestationally treated with cocaine are compulsively aggressive and aggression is significantly elevated in nontreated rat mothers when amygdaloid oxytocin receptors are blocked during the postpartum period Lubin, Elliott et al, 2003). Increases in oxytocin levels in brain regions of the postpartum rat, such as the medial preoptic area of the hypothalamus, ventral tegmental region, and amygdala, are associated with better maternal behavior and, for amygdala only, decreased aggression (Elliott et al, 2001;Johns et al, 1998).…”

“…Continuing exposure to postpartum cocaine may result in somewhat different patterns of disruptions in maternal behavior or aggression depending on dose and frequency of use during pregnancy (Johns, Lubin, Walker, Meter, & Mason, 1997;Johns, Noonan, Zimmerman, Li, & Pedersen, 1997;Johns et al, 2002;. These abnormal maternal behaviors appeared to be at least partially mediated by cocaine-induced changes in oxytocin activity (Elliott, Lubin, & Johns, 2001;Johns, Lubin et al, 1997;Lubin, Elliott, Black, & Johns, 2003).…”

Cocaine treatment and prenatal environment interact to disrupt intergenerational maternal behavior in rats.

“…In previous studies, dams treated with cocaine gestationally were also found to exhibit differences in oxytocin system dynamics Johns, Lubin, Walker, Meter, & Mason, 1997;Johns, Nelson, et al, 1998;; Lubin, Elliott, Black, & Johns, 2003). Oxytocin is an important neuroendocrine system implicated in normal maternal behavior onset in rats (Fuchs, 1983;Pedersen et al, 1982;Pedersen, Caldwell, Johnson, Fort, & Prange, 1985;Pedersen et al, 1994) and therefore likely to be implicated when this behavior is disrupted (Pedersen et al, 1985; Van Leengoed, Kerker, & Swanson, 1987).…”

“…Significant disruptions in maternal behavior following chronic gestational cocaine treatment during pregnancy were reported for the onset or very early post-partum period, and these dams did not display the hyperactivity often seen in acutely treated dams (Heyser, Molina, & Spear, 1992;Kinsley et al, 1994;Peeke, Dark, Salamy, Salfi, & Shah, 1994; Vernotica, Lisciotto, Rosenblatt, & Morrell, 1996). No reports, to our knowledge, have been published on intermittent gestational and postpartum cocaine treatment or the intergeneration effects of such treatment on maternal behavior.In previous studies, dams treated with cocaine gestationally were also found to exhibit differences in oxytocin system dynamics Johns, Lubin, Walker, Meter, & Mason, 1997;Johns, Nelson, et al, 1998;; Lubin, Elliott, Black, & Johns, 2003). Oxytocin is an important neuroendocrine system implicated in normal maternal behavior onset in rats (Fuchs, 1983;Pedersen et al, 1982;Pedersen, Caldwell, Johnson, Fort, & Prange, 1985;Pedersen et al, 1994) and therefore likely to be implicated when this behavior is disrupted (Pedersen et al, 1985; Van Leengoed, Kerker, & Swanson, 1987).…”