EFFECTS OF AMPHETAMINE, COCAINE, AND EPHEDRINE ON THE SEDATIVE AND HYPOTENSIVE ACTION OF RESERPINE IN RABBIT

Abstract

The effects of reserpine on the behavior of the intact rabbit and on the pressor responses of the urethanized rabbit to hypothalamic, thalamic and splanchnic stimulations were studied. The intravenous injection of 1.0 mg/kg of resperine gradually manifested a characteristic sedation and a depression or abolition of the pressor responses, and these depressive effects were most prominent 10 to 20 hours after the injection. Pretreatment of the animal with iproniazid (50 to 100 mg/kg intraperitoneally, 24 hours previously), amphetamine (0.5 to 1.0 mg/kg intravenously, 30 minutes to one hour previously), cocaine (2.0 mg/kg intravenously, 30 minutes previously) or ephedrine (0.5 mg/kg intravenously, 30 minutes previously) modified the response to reserpine. The injection of reserpine caused motor excitement with an increased sympathetic activity in the animal pretreated with one of these agents. Ten to 20 hours later, the animal was in a state of sedation, however, the animal responded with motor movements for a while to nociceptive mechanical stimuli. The blood pressure was raised transiently in the early stage of the intravenous injection of reserpine. Ten to 20 hours later, a depression or abolition of the pressor responses was seen. The intracarotid injection of 0.1 mg/kg of reserpine did not manifest sedation nor excitation even 10 to 20 hours after the injection of reserpine. The pressor responses were also not significantly modified. Rabbits which were pretreated with the intracarotid injection of amphetamine (0.05 to 0.1 mg/kg, 1 hour), cocaine (0.2 mg/kg, 1 hour) or ephedrine (0.05 mg/kg, 1 hour) showed a motor excitement with an increased sympathetic activity as the response to the animal fell into a state of sedation, during which nociceptive mechanical stimulation could awake the animal and induce motor movement for a while. The pressor responses to thalamic and hypothalamic stimulation of the animal pretreated with amphetamine, ephedrine or cocaine intra-carotidally were markedly depressed, and after repetition of the stimulation the responses completely disappeared, while the response to splanchnic stimulation was not modified. The hypersensitivity of the pressor response to epinephrine or norepinephrine in the animal which received reserpine intravenously or intracarotidally was not significantly modified by pretreatment with iproniazid, amphetamine, cocaine or ephedrine.