Functional consequences of acute cocaine treatment depend on route of administration

Publisher Website
Google Scholar
Abstract
The 2-[14C]deoxyglucose method was used to compare the effects of the acute administration of cocaine by two different routes, intravenous and intraperitoneal, on rates of local cerebral glucose utilization in freely moving rats. Doses were initially chosen on the basis of their ability to elicit equivalent increases in locomotor activity during the experimental procedure, and the time of cocaine administration relative to 2-[14C]deoxyglucose infusion was chosen so that the maximal behavioral effect occurred during maximal tracer incorporation. Changes in glucose utilization following the intraperitoneal administration of cocaine (10 mg/kg, 10 min before 2-deoxyglucose infusion) were restricted to the nigrostriatal system and related structures involved in the production of movement. Increased activity was observed in the substantia nigra pars reticulata, globus pallidus, and sensorimotor cortex. In contrast, intravenous cocaine administration (1 mg/kg, 2 min before tracer infusion) produced more widespread changes in rates of glucose utilization including portions of both the mesocorticolimbic and nigrostriatal systems. Areas in which metabolic activity was altered included the caudate-putamen, globus pallidus, substantia nigra pars reticulata, sensorimotor cortex, olfactory tubercle, nucleus accumbens, and medial prefrontal cortex. Both intravenous and intraperitoneal cocaine produced similar increases in locomotor activity. Additional studies indicated that the absence of metabolic activation in the mesocorticolimbic system following acute intraperitoneal cocaine was not the result of the specific dose chosen or the length of time between cocaine administration and radiotracer infusion, as no changes in metabolic activity in mesocorticolimbic structures were evident when these parameters were varied. The cerebral metabolic effects of acute intravenous and intraperitoneal cocaine administration are significantly different. These data indicate that pharmacokinetic variables are important determinants of the functional response to cocaine.