Behavioral and biochemical changes induced by lithium and L-tryptophan in muricidal rats

Lithium (0.5--12 meq/kg) and L-tryptophan (100--800 mg/kg) inhibited the muricidal (mouse killing) response in isolated, male, Long Evans rats and did so both in an acute (single dose) and on an longer-term intraperitoneal treatment basis. The response was dose-dependent. There was no concomitant motor impairment at doses effective in inhibiting the muricidal response. Plasma lithium levels were positively correlated with the percentage inhibition of muricidal behavior. When lithium and L-tryptophan were administered in combination in their smallest effective doses, the behavioral interaction was synergistic in the acute and addictive in the longer-term treatment. The effects of pharmacological treatment on the inhibition of muricidal behavior were: lithium and L-tryptophan greater than L-tryptophan greater than - lithium. The results of biochemical assays showed that these compounds fore- and hindbrain serotonin turnover. The biochemical action of lithium and L-tryptophan in combination on brain serotonergic pathways was again clearly more potent than that which occurred after treatment with either lithium or L-tryptophan alone. The magnitude of the biochemical changes paralleled those of psychopharmacological changes. These data show an interaction between lithium and L-tryptophan both in the repression of aggressive behavior in rats and in the alteration of centrally acting serotonergic function. These data further elucidate a mechanism of action through central serotonergic function for a psychotherapeutic agent, lithium, and for aggressive behavior, muricide.