Separate Mechanisms for Behavioral, Cardiovascular, and Hormonal Responses to Dextroamphetamine in Man

The neurochemical specificity of physiological, biochemical, and psychological responses to dextroamphetamine was tested by pretreating volunteers with haloperidol (0.014 mg/kg IM), propranolol (0.1 mg/kg IV), thymoxamine (0.1 mg/kg IV), or placebo prior to 0.3 mg/kg IV amphetamine. Healthy volunteers (N = 12) participated in the studies, but not all volunteers received each drug combination. Haloperidol prevented dextroamphetamine-induced behavioral excitation, but did not significantly affect plasma norepinephrine or pressor responses, whereas propranolol inhibited norepinephrine and pressor responses without influencing excitation or other behavioral responses. Thymoxamine did not affect any of the responses measured. None of the agents significantly affected plasma cortisol or growth hormone responses. The prolactin rise following dextroamphetamine was potentiated by haloperidol. The results are consistent with the hypothesis that behavioral excitation after dextroamphetamine occurs through a dopaminergic mechanism, and pressor responses through a noradrenergic mechanism.