Understanding and Preventing Violence, Volume 2: Biobehavioral Influences (1994)
Chapter: Noradrenergic and Serotonergic Reuptake Blockers and MAO Inhibitors
Noradrenergic and Serotonergic Reuptake Blockers and MAO Inhibitors
The most consistent effect of antidepressant drugs in animal preparations is the blockade of killing behavior in laboratory rats (see Table 8A). The efficacious and potent suppression of mouse killing (antimuricidal effect) by drugs that are clinically useful as antidepressants is exploited as a screening device in drug development research, but has provided little insights into the neurobiology of killing behavior. The antimuricidal effect is seen with relatively low doses of antidepressants that act either by noradrenergic or serotonergic reuptake inhibition or as MAO inhibitors (e.g., Horovitz et al., 1966; Valzelli and Bernasconi, 1976; Shibata et al., 1984). Microinjection studies suggest the amygdala and the posterior and lateral hypothalamus as the most effective sites for tricyclics to achieve blockade of killing behavior in rats and cats (Leaf et al., 1969; Dubinsky et al., 1973; Watanabe et al., 1979; Hara et al., 1983). The neurobiologic mechanisms for killing behavior by rats and those for predatory killing by carnivores appear to differ. Blockade of noradrenergic or serotonergic uptake sites by tricyclic antidepressants or by fluoxetine does not modulate predatory killing by cats or ferrets (Karli et al., 1968; Leaf et al., 1978; Schmidt, 1979, 1980; Schmidt and Meierl, 1980). These findings question to what extent antidepressant blockade of killing by rats can be extrapolated to killing behavior in other animal species or possibly humans.
As summarized in Table 8A, much of the work with experimental preparations of animal aggression and antidepressants has employed acute administration of these drugs. The clinical relevance of this considerable literature is to caution against the use of tricyclics or MAO inhibitors in acute emergencies for controlling violent individuals. The studies in animals prove these agents not to be particularly selective or reliable in decreasing aggressive responses. Acute administration of tricyclic as well as MAO-inhibiting antidepressants most often decreased aggressive behavior of isolated mice, rats in competition tests, or rats rendered irritable by neurotoxicity or neural lesions, often only at sedative and motor-impairing doses (e.g., DaVanzo et al., 1966; Sofia, 1969b; Isel et al., 1988; Isel and Mandel, 1989). Antidepressants with 5-HT reuptake-blocking properties decrease aggressive elements of behavior, but increase defensive responses in several animal preparations (Table 8A; e.g., Poshivalov, 1981; Olivier and van Dalen, 1982; Carlini and Lindsey, 1982). Antidepressants, especially when
