On the role of central nervous system catecholamines and 5-hydroxytryptamine in the nialamide-induced behavioural syndrome

Abstract

1. Intraperitoneal administration of nialamide, 200 mg/kg, to mice elicited a pronounced increase in motor activity and rectal temperature concomitant with a gradual increase in the concentrations of 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine in the brain.2. In mice treated with L-tryptophan, 300 mg/kg, 1 h before nialamide, the increase in motor activity appeared earlier than after nialamide alone, and the hyperthermia was more pronounced. The increase in 5-HT concentrations in the brain was more pronounced in these animals, whereas the concentrations of NA and dopamine were of the same magnitude as after nialamide alone.3. Treatment with p-chlorophenylalanine methylester-HCl (PCPA), 400 mg/kg, 24 h before nialamide partially antagonized the increase in motor activity and the accumulation of NA and dopamine was not significantly different from that observed after nialamide alone.4. Treatment with PCPA, 800 mg/kg, 72, 48 and 24 h before nialamide, completely antagonized the increase in motor activity and rectal temperature. The accumulation of brain 5-HT was greatly depressed in these animals. The concentrations of dopamine 1, 3 and 6 h and the concentration of NA 6 h after the nialamide injection were significantly lower in the mice given PCPA 800 mg/kg x 3, than in the mice given nialamide alone.5. Administration of DL-5-hydroxytryptophan, 30 mg/kg, 1 h after the nialamide injection, to mice pretreated with PCPA, 800 mg/kg x 3, restored the increase in motor activity and rectal temperature.6. L-Tryptophan, 300 mg/kg, given 1 h before nialamide to mice pretreated with PCPA, 800 mg/kg x 3, elicited a moderate increase in motor activity and a slight increase in the accumulation of 5-HT in the brain when compared to that after PCPA, 800 mg/kg x 3, and nialamide.7. Administration of alpha-methyltyrosine methylester, 200 mg/kg, 2 h before nialamide partially antagonized the increase in motor activity and completely antagonized the increase in rectal temperature elicited by nialamide alone. The accumulation of brain NA and dopamine was inhibited in these animals.8. It is concluded that the excitation in mice, elicited by nialamide, is mediated largely via brain 5-HT, but that also the brain catecholamines seem to contribute to this effect.