Factors determining whether cocaine will potentiate the cardiac effects of neurally released norepinephrine

The purpose of the present study was to re-evaluate the effects of cocaine on cardiac responses elicited by sympathetic nerve stimulation. Cats anesthetized with pentobarbital and subjected to spinal cord transection were used. Control heart rate increases were obtained to submaximal stimulation of postganglionic accelerator nerves, before and after i.v. bolus doses of cocaine ranging from 0.0625 to 2.0 mg/kg. Maximal potentiation of heart rate increases elicited by nerve stimulation were observed with 0.25 mg/kg. In precocaine controls, stimulation increased sinus rate by 31 +/- beats/min; 30 sec to 1 min after cocaine (0.25 mg/kg), stimulation increased sinus rate by 55 +/- beats/min. Maximal potentiation (80 +/- 10%) was observed at 30 sec to 1 min after cocaine administration, and was usually over by 45 to 60 min later. Cocaine was repeated twice (0.25 mg/kg i.v.) at hourly intervals and the magnitude of potentiation was only 19 +/- 6 and 24 +/- 4%, respectively, indicating that tachyphylaxis had developed toward cocaine's potentiating effect. Dose-response studies indicated that as little as 0.0625 mg/kg of cocaine can potentiate heart rate increases elicited by sympathetic nerve stimulation. Doubling the dose to 0.125 mg/kg, and again to 0.25 mg/kg, resulted in a linear dose-related increase in the magnitude of potentiation. However, doubling the dose again to 0.5 mg/kg and increasing this dose by 4-fold to 2 mg/kg did not result in additional potentiation. Indeed, there was a significant drop-off in the magnitude of potentiation to nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)