Understanding and Preventing Violence, Volume 2: Biobehavioral Influences (1994)
Chapter: Gaba Correlates of Animal Aggression
amygdaloid, striatal, and cortical areas. It is highly problematic to generalize from single peripheral measures such as blood or CSF 5-HIAA to the complexity of 5-HT activity in a violent or aggressive individual. At the cellular level, pharmacologic manipulations that impair presynaptic events such as precursor uptake, synthesis, storage, release or metabolism, increase the probability of the muricidal reaction and, less reliably, of defensive responses in rats. By contrast, postsynaptic 5-HT receptor manipulations, particularly at the 5-HT 1A subtype, are effective antiaggressive drugs in animal models (see below). An important qualification of the results from animal models of aggression is the impressive evolutionary variation in 5-HT functions, rendering extrapolation from a specific animal species to another one, including human, problematic.
GABA
At the cellular level, GABA causes hyperpolarization of neurons the mammalian central nervous system, primarily in short inhibitory interneurons. Whether or not this inhibitory role at the cellular level, occurring in about one-third of the synapses in the brain, nay be extrapolated to the behavioral level remains unknown, although it has been postulated with regard to aggression (e.g., Mandel et al., 1981). During the past decade, the study of GABA receptors intensified when it was discovered that benzodiazepine-type anxiolytic drugs achieve their physiologic and behavioral effects by action on a supramolecular benzodiazepine receptor-GABAA-chloride ionophore complex. Before discussing the pharmacotherapeutic applications and associated risks of these types of drugs in the management of violent patients, it will be useful to summarize the evidence on GABA, aggression, and violence in animals and in humans (see Table 4).
GABA AND AGGRESSION
Gaba Correlates of Animal Aggression
Several neurochemical studies found an inverse relationship between brain GABA levels, particularly in the olfactory bulb and striatum, and aggressive behavior in mice (Table 4, section A; Earley and Leonard, 1977; Simler et al., 1982). Also, GABA content in olfactory bulbs of muricidal rats was lower than in nonkiller rats (Mack et al., 1975; Mandel et al., 1979). Lower GABA content
