Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression.

1. Violence and aggression are major public health problems. 2. The authors have used techniques of electrical brain stimulation, anatomical-immunohistochemical techniques, and behavioral pharmacology to investigate the neural systems and circuits underlying aggressive behavior in the cat. 3. The medial hypothalamus and midbrain periaqueductal gray are the most important structures mediating defensive rage behavior, and the perifornical lateral hypothalamus clearly mediates predatory attack behavior. The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area, cingulate gyrus, and prefrontal cortex project to these structures directly or indirectly and thus can modulate the intensity of attack and rage. 4. Evidence suggests that several neurotransmitters facilitate defensive rage within the PAG and medial hypothalamus, including glutamate, Substance P, and cholecystokinin, and that opioid peptides suppress it; these effects usually depend on the subtype of receptor that is activated. 5. A key recent discovery was a GABAergic projection that may underlie the often-observed reciprocally inhibitory relationship between these two forms of aggression. 6. Recently, Substance P has come under scrutiny as a possible key neurotransmitter involved in defensive rage, and the mechanism by which it plays a role in aggression and rage is under investigation. 7. It is hoped that this line of research will provide a better understanding of the neural mechanisms and substrates regulating aggression and rage and thus establish a rational basis for treatment of disorders associated with these forms of aggression.

Neuropharmacology of brain-stimulation-evoked aggression.

Evidence is reviewed concerning the brain areas and neurotransmitters involved in aggressive behavior in the cat and rodent. In the cat, two distinct neural circuits involving the hypothalamus and PAG subserve two different kinds of aggression: defensive rage and predatory (quiet-biting) attack. The roles played by the neurotransmitters serotonin, GABA, glutamate, opioids, cholecystokinin, substance P, norepinephrine, dopamine, and acetylcholine in the modulation and expression of aggression are discussed. For the rat, a single area, largely coincident with the intermediate hypothalamic area, is crucial for the expression of attack; variations in the rat attack response in natural settings are due largely to environmental variables. Experimental evidence emphasizing the roles of serotonin and GABA in modulating hypothalamically evoked attack in the rat is discussed. It is concluded that significant progress has been made concerning our knowledge of the circuitry underlying the neural basis of aggression. Although new and important insights have been made concerning neurotransmitter regulation of aggressive behavior, wide gaps in our knowledge remain.

Dependence of rat vertex auditory evoked potentials on central muscarinic receptor activation.

Auditory evoked potentials (AEPs) were recorded epidurally at vertex in the freely moving rat, yielding the prominent components P18 and N40 from the average waveform. Both components were severely attenuated at tone presentation rates faster than 1 Hz. Dependence of the vertex AEP on central cholinergic activation was assessed by comparing the effects of subcutaneous injections of the muscarinic antagonist scopolamine (0.1-1.0 mg/kg) to methyl-scopolamine (0.5, 1.0 mg/kg) to test for peripheral effects. Scopolamine produced a significant decrease in amplitude for both the P18 and N40 components in overall tests. N40 amplitude also showed a significant decrease at each dose of scopolamine, and the magnitude of the amplitude decrement was dose dependent. At 23 h after scopolamine, only N40 amplitude remained significantly depressed. There were no effects of injection of saline, or of methyl-scopolamine. These results confirm that middle-latency vertex AEPs in the rat are attenuated by central muscarinic receptor blockade, consistent with previous findings in cats.