Understanding and Preventing Violence, Volume 2: Biobehavioral Influences (1994)
Chapter: SEROTONIN
1970, 1971a; Rolinski, 1975; Berzsenyi et al., 1983; Molina et al., 1987; Isel and Mandel, 1989). Although the literature on human violence uses the term "predatory" in analogy to stalking and killing in carnivorous animal species, the relationship between the predatory behavior of certain animal species and human aggressive or violent behavior remains to be explored.
Dopamine receptor antagonists have been studied extensively for their antiaggressive effects; however, their selectivity as antiaggressive drugs remains unsatisfactory (e.g., Eichelman, 1986; Miczek, 1987; Miczek et al., 1994). Most of these substances have been developed as potential antipsychotic or neuroleptic drugs, and this literature is reviewed below (Table 7). Recently, selective antagonists for D1 and D2 receptors have been developed (e.g., McMillen et al., 1989; Redolat et al., 1991). Initial evidence indicates that blockade of either dopamine receptor subtype potently decreases aggressive behavior in mice and monkeys, albeit with limited behavioral specificity (Ellenbroek and Cools, 1990; Tidey and Miczek, 1992; Miczek et al., 1994). Future studies will have to identify the dopamine receptor populations that are most relevant in the initiation and execution of aggressive and defensive behavior patterns in animals in order to develop a rational basis for clinical trials in humans.
The successful use of beta-adrenergic receptor blockers in the management of violent patients identifies these substances as potential therapeutic options (e.g., Ratey et al., 1986, 1987). The clinical evidence on beta-blockers is reviewed below. When the prototypical beta-blocker, propranolol, was found to be beneficial in calming violent individuals who are unresponsive to other medications (e.g., Elliott, 1977), its therapeutic value was thought to derive from its blockade of noradrenergic beta-receptors. In the meantime, propranolol, pindolol, nadolol, and similar substances, which have been found to show high affinity for 5-HT1A, act as antagonists (Olivier et al., 1990), and it is this serotonergic mechanism of action that may be the basis for the antiaggressive effects of beta-blockers.
SEROTONIN
No other neurotransmitter has been more intimately implicated in the neurobiologic mechanisms of aggressive and violent behavior than 5-HT (e.g., Brown et al., 1979; Valzelli, 1981; van Praag et al., 1987; Roy and Linnoila, 1988; Coccaro, 1989; Miczek and Donat, 1989). A major theme in the biological psychiatry
