Spatial and temporal distribution of cocaine and effects of pharmacological interventions: wholebody autoradiographic...

Whole body timed distribution of pharmacological doses of 14C-cocaine was studied in rats using quantitative autoradiographic microimaging. Rapid, intense uptake was seen in the brain, spinal cord, adrenals and nuchal brown fat pad. Clearance of cocaine was fastest from the cerebellum. Cortex activity reached soft tissue activity within 20 min. Uptake in the heart and adrenals was very intense following the same time course as in the brain. Kidney activity increased gradually at the same time as in the liver, probably representing specific binding as well as an excretory pathway of cocaine. Desipramine decreased uptake in the heart and adrenals and a piperazine derivative (GBR 12909) caused decreased uptake in the brain, heart and adrenals. Scopolamine, pentobarbital and cold cocaine caused decreased uptake in all organs and increased uptake (excretion) in the liver. Thus, cocaine appears to bind in the brain to the dopamine transporter and to a lesser extent to transporters for norepinephrine and serotonin. In the heart cocaine binds to norepinephrine, serotonin and dopamine. The targeting of cocaine to specific organs and the time sequence correspond to the pharmacological effects of cocaine.