Burr Eichelman

Facilitation of shock-induced fighting following intraventricular 5,7-dihydroxytryptamine and 6-hydroxydopa

Using a 15-s intershock interval, an increase in shock-induced fighting was observed following intraventricular 96 μg 5,7-dihydroxytryptamine (5,7-DHT) and 90 μg 6-hydroxydopa (6-OHdopa). The incidence of predatory mouse killing was enhanced by 5,7-DHT, but was not affected by 6-OHdopa. Pain sensitivity was increased by 6-OHdopa, but both neurotoxins produced hyperreactivity to footshock. Specific serotonin depletion was produced by 5,7-DHT and norepinephrine depletion by 6-OHdopa. The increase in shock-induced fighting could not be predicted on the basis of monoamine depletion alone, since a long intershock interval was necessary to observe this increase.

Effects of dietary supplements and a tryptophan-free diet on aggressive behavior in rats ☆

The effects of dietary excesses of tryptophan, histidine, tyrosine or choline and of a tryptophan-free diet were examined on shock-induced fighting, muricide and jump-flinch thresholds. Following the tryptophan-free diet, shock-induced fighting and pain sensitivity were specifically increased. The increased incidence of muricide was not specific to the lack of tryptophan in the diet. Groups of rats which were pair fed chow or had 0.15% L-tryptophan added to the tryptophan-free diet increased muricide as well. Brain 5-HT levels were 41% depleted following the tryptophan-free diet and reduced 13% with the 0.15% tryptophan supplement. In addition body weights were reduced in the three groups compared to control. None of the excess diets affected shock-induced fighting, muricide and jump-flinch thresholds. Body weights were decreased in the excess tryptophan, histidine, tyrosine and choline groups. These data indicate that the expression of different forms of aggression appears to be influenced by a tryptophan deficiency in the diet, but not by excesses of tryptophan, tyrosine, histidine and choline.

Dietary tryptophan modulation and aggressive behavior in mice

The effects of a tryptophan-free diet on isolation-induced fighting and predatory cricket killing in mice were examined. The results demonstrated that consumption of a tryptophan-free diet for 18-20 days decreased both the number of fighters and duration of isolation-induced fighting; increased the number of cricket-killing mice and decreased the latencies to attack and the latencies to kill crickets; reduced brain serotonin 27%; increased water intake 38%; and decreased body weight 27% without affecting food intake. To determine if these effects were due specifically to the lack of dietary tryptophan, other groups of mice were fed a 5% tryptophan load in the standard chow; a 0.15% tryptophan supplement in the tryptophan-free diet; or a 3 grams/day restricted chow diet. The lack of tryptophan in the diet produced the marked inhibition in isolation-induced fighting, the reduction in brain serotonin, and the large decrease in body weight. The other non-specific effects appeared to be related to general factors such as dietary need for the cricket killing or diet composition (other than the lack of tryptophan) for the water intake.

The limbic system and aggression in humans

This paper reviews the clinical literature relevant to the association between aggressive behavior and the limbic system in humans. Specific areas of review include aggressive behavior related to: (1) naturally occurring and iatrogenic brain lesions; (2) electrical disturbances; (3) pharmacologic intervention; and (4) central neurochemical concentrations which may implicate limbic lobe involvement.

Dietary tryptophan reversal of septal lesion and 5,7-DHT lesion elicited shock-induced fighting

Using two procedures known to enhance shock-induced defensive fighting (SIF) and mouse-killing--septal lesions and 5,7-DHT lesions--we determined if a 5% tryptophan-loaded diet could reverse the lesion effects. The results indicated that SIF, but not mouse-killing, could be maintained at normal levels following dietary tryptophan loading in both septally lesioned and 5,7-DHT lesioned rats. This behavioral reversal was independent of pain sensitivity, feeding, drinking and body weight levels. Regional brain analysis of monoamines and metabolites indicated that the lesions produced substantial depletions in 5-HT and 5-HIAA with minimal reduction or no change in catecholamines. Dietary tryptophan loading elevated 5-HT and 5-HIAA in unlesioned animals and partially restored 5-HT and 5-HIAA levels in lesioned animals. These patterns of depletion and repletion were confined to the hippocampus following septal lesions and distributed throughout the brain following 5,7-DHT lesions. The results are discussed in terms of a possible hippocampal mediation of the dietary tryptophan reversal in shock-induced defensive fighting following lesioning.

Variability in rat irritable and predatory aggression

Rats from differing strains and/or suppliers show marked differences in the stability and frequency of shock-induced fighting under uniform parameters. Similar differences occur in mouse-killing behavior. Aggression differences are not necessarily related to differences in footshock sensitivity. Such behavioral variability can be used to correlate strain-dependent neurochemical and behavioral characteristics.

Regional changes in monoamines and metabolites following defensive aggression in the rat.

Pharmacological studies have demonstrated that shock-induced defensive fighting is modulated by manipulations of the serotonergic, noradrenergic and dopaminergic neurotransmitter systems. In the present study, regional changes in 5- hydroxytryptamine , norepinephrine, dopamine and their metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol and 3,4-dihydroxyphenylacetic acid were measured following shock-induced fighting using high performance liquid chromatography coupled with electrochemical detection. Fighting produced reductions in the serotonergic, noradrenergic and dopaminergic systems and elevations in the noradrenergic and dopaminergic systems within the brain stem, hypothalamus, hippocampus, caudate and amygdala relative to shocked or non-shocked controls. These data demonstrate that the activities of these neurotransmitters are involved in defensive aggression in rats. The changes in catecholamines may indicate adaptive responses to stress, while the changes in serotonin may indicate a permissive function for serotonin depletion in defensive fighting.

Aggression-altering effects of cyclic AMP

Abstract Dibutyryl cyclic AMP, infused intraventricularly in rats and mice, produced dosedependent increases in cyclic AMP and dose-dependent decreases in shock-induced rat fighting and isolation-induced mouse fighting and cricket attack, but not in cricket killing or mouse killing. Reduction in aggression with 25 μg was not related to sedation or motor disturbance since motor activity counts were normal, as were whole brain levels of serotonin, norepinephrine, and dopamine. These data are consistent with the hypothesis that neuronal cyclic AMP, in part, functions as a second messenger mediating the effects of released neurotransmitters in regulating behavior.

L-histidine-induced facilitation of cholesterol biosynthesis in rats.

Summary A diet supplemented 5% with L-histidine induces hypercholesterolemia in rats. To examine the mechanism involved, L-histidine was added to either a chow or fat-free diet and fed to rats for 18 days. After 2 days of fasting, the rats were refed the same diet for three days. There was a ninefold increase in the incorporation of [14C] acetate into the nonsaponifiable fraction in the 5,000g hepatic fraction of histidine-supplemented chow-fed rats compared to controls. The increase in the incorporation of the labeled substrate into the digitonin-precipitable fraction was seven- to eightfold. The incorporation of [14C]mevalonate was increased by sevenfold in both the nonsaponifiable and digitonin-precipitable fractions. Longterm histidine supplementation to fat-free diet did not affect the incorporation of either [14C] acetate or [14C] mevalonate into these fractions. We wish to thank Ms. Cynthia Birch for her technical assistance.

Cyclic nucleotides and aggressive behavior.

Cyclic nucleotides, particularly cyclic AMP, have been implicated as second messengers in neuronal activity. Attempts to demonstrate an association between endogenous cAMP or cGMP levels and rodent aggressive behavior have been only partially successful. Low levels of cAMP in rodent brain appear associated with lower levels of affective aggression. Consistent with this possible relationship is our finding that the infusion of dibutyryl cAMP into rodent cerebroventricles decreases aggressive behavior. The infusion of dibutyryl cyclic GMP, conversely, facilitates shock-induced fighting in the rat.