Runway self-administration of intracerebroventricular cocaine: evidence of mixed positive and negative drug actions

Abstract

In previous work from our laboratory, animals running for intravenous cocaine developed a unique approach-avoidance 'retreat behavior' that was hypothesized to result from cocaine's well documented reinforcing (positive) and anxiogenic (negative) properties. To assess the role of central mechanisms in producing cocaine's positive and negative effects, we assessed whether or not animals running a straight alley for intracerebroventricular applications of cocaine would produce a similar behavioral profile to that previously observed with intravenous applications. Retreat frequency and location were measured in male Sprague-Dawley rats trained to run an alley for one of four doses of intracerebroventricular-administered cocaine (0, 25, 50 or 100 microg cocaine/infusion). Testing involved a single trial per day over 14 consecutive days with a single infusion of cocaine delivered upon goal box entry. The 100 and 50 microg intracerebroventricular cocaine groups exhibited significantly higher retreat frequencies than the 25 and 0 microg groups and the nature and magnitude of the behavior was comparable to that previously observed with intravenous cocaine. These results suggest that the intracerebroventricular self-administration of cocaine results in mixed positive and negative consequences and therefore likely stem from the drug's actions within the central nervous system.