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.
D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001711:Biotransformation; D001923:Brain Chemistry / Q000187:drug effects*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008094:Lithium / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D008094:Lithium