AMPHETAMINE TOXICITY AND BRAIN MONOAMINES IN 3 MODELS OF STRESS

After exposure of rats to cold-stress, drum-stress, or electric shock-stress, the intraperitoneal LD50 of d-amphetamine was found to be 34.5, 6.1, and 0.9 mg/kg, respectively, in contrast to an LD50 value of 63.5 mg/kg in nonstressed animals. None of the stresses used significantly altered the level of brain stem norepinephrine. However, these levels fell more rapidly after the injection of l-α-methyltyrosine in stressed animals than in nonstressed controls, suggesting a faster turnover rate of this amine. A significant increase in the level of brain stem serotonin was obtained following drum- or electric shock-stress, but not after cold-stress. This increase was obtained in animals subjected to stress alone, or those given the highest possible nonlethal dose of amphetamine. These same doses did not augment the catecholamine-releasing properties of amphetamine in drum- or electric shock-stressed animals. It does not appear that stress potentiates the effects of amphetamine, as no evidence of excitation was obtained in stressed animals given amphetamine. It is postulated that amphetamine enhances the effects of stress. The interrelationships with chlorpromazine, dibenamine, tetrabenazine, chlordiazepoxide, and l-α-methyltyrosine are presented. © 1969.