Heightened drug-seeking motivation following extended daily access to self-administered cocaine

Rats allowed extended daily access (6 h) to cocaine, consume high doses of the drug and escalate their cocaine intake over days, resembling the pattern of cocaine use seen in human addicts. The current study was designed to test whether such animals would also demonstrate the heightened motivation to seek cocaine seen in human addicts. Rats were trained to lever press for i.v. cocaine (0.25 mg/infusion) over a 5-day period of 1 h sessions. Subjects were then assigned to either a brief-access (1 h/day) or an extended-access condition for an additional 10 days. Control rats lever pressed for i.v. saline. Following the final self-administration session animals were tested for their motivation to receive cocaine in an operant runway apparatus. Extended-access animals exhibited significantly higher motivation for cocaine in the runway (where they received 1.0 mg/kg cocaine i.v. upon goal-box entry) as was evident by faster run times and less ambivalence about entering the goal box (i.e. retreat behavior) than either brief-access or control subjects. Brief and extended-access animals, tested in the Elevated Plus Maze, exhibited comparable and significant increases in anxiety following a single 1.0 mg/kg i.v. injection of cocaine, as compared to saline control animals that were challenged with i.v. saline infusion. Together, these data suggest that extended access to cocaine results in an especially high motivation for the drug that is not accounted for by reductions in the anxiogenic properties of cocaine. (c) 2008 Elsevier Inc. All rights reserved.