The effect of a bovine hypothalamic factor on mouse brain neurotransmitters

A substance isolated from the bovine hypothalamus was found to protect against the toxicity of amphetamine in the crowded mice situation. We measured the levels of brain catecholamines (norepinephrine and dopamine) and γ-aminobutyric acid during crowding following the administration of amphetamine, hypothalamic factor, and amphetamine + hypothalamic factor simultaneously. Amphetamine at high dosage (20mg/kg) decreased brain norepinephrine (25%), had no effect on dopamine and increased γ-aminobutyric acid levels (78%). Hypothalamic factor (1.0 ml) increased both norepinephrine and dopamine concentrations (51% and 37%, respectively) but had little effect on γ-aminobutyric acid levels. Simultaneous administration of both agents resulted in a decrease in norepinephrine (similar to that seen with amphetamine alone), an increase in dopamine (the same as seen with hypothalamic factor alone), and caused a marked decrease in brain γ-aminobutyric acid levels.The reversal of amphetamine toxicity suggests that the hypothalamic factor may act centrally at the neuronal level. The lethality of amphetamine in the crowded mice situation may be due, in part, to the high level of γ-aminobutyric acid in the brain and which was reversed in the presence of the hypothalamic factor.