Increased plasma corticosterone, aggressiveness and brain monoamine changes induced by central injection of pertussis toxin.

The effects of intracerebroventricular (i.c.v.) injection of pertussis toxin, a specific inhibitor of G(i)/G(o) proteins, on plasma corticosterone levels, aggressiveness, and hypothalamic and hippocampal monoamines and their metabolites levels were examined in mice. Plasma corticosterone level was markedly increased at 3 h after pertussis toxin injection (0.03 and 0.2 microg/mouse), peaked at 6 h and was still increased for up to 6 days after injection. Mice injected with pertussis toxin (0.2 microg/mouse) did not show weight gain between day 0 and day 6 after injection. In addition, pertussis toxin (0.2 microg/mouse) induced a progressive increase in aggressiveness, i.e. a decrease in attack latency and an increase in number of attacks, on day 1 and 6 after injection. Brain monoamines and their metabolites levels were changed on day 1 and 6 after pertussis toxin injection (0.2 microg/mouse): in the hypothalamus, levels of dopamine and 3,4-dihydroxyphenylacetic acid were increased, norepinephrine level decreased, and 5-hydroxyindole acetic acid (5-HIAA) level was markedly increased, with no changes in 5-hydroxytryptamine (5-HT) level, whereas in the hippocampus, 5-HT level was significantly decreased, with no changes in 5-HIAA and catecholamines. These results suggest that signal transduction through G(i)/G(o) proteins in the brain is involved in the modulation of hypothalamo-pituitary-adrenal axis, aggressiveness, and monoamine levels in vivo.