Behavioral sensitization to cocaine in the absence of altered brain cocaine levels

We conducted experiments investigating the role of altered cocaine distribution in behavioral sensitization. The first was designed to determine whether carry-over from one injection to the next occurs after acute cocaine administration. Female, Sprague-Dawley rats were administered 5 mg/kg 3H-cocaine and 24 h later were challenged with either 5 mg/kg unlabeled cocaine or saline. Animals were sacrificed 15 min after drug administration. There was no difference between groups in cocaine levels in brain, liver, or plasma, thus indicating that carry-over did not occur following acute cocaine administration. The second experiment was designed to determine whether bound cocaine could be released following acute or multiple dose cocaine administration. In the acute dose study, animals were administered either 20 mg/kg cocaine or saline, challenged 24 h later with 5 mg/kg 3H-cocaine, and sacrificed 5 min after drug administration. Animals with previous cocaine experience exhibited a significant increase in the number of rearings. The groups did not differ in brain or plasma cocaine levels. In the multiple dose study, animals were injected daily for 4 days with 20 mg/kg cocaine or saline, challenged with 5 mg/kg 3H-cocaine on day 5, and sacrificed 10 min after drug administration. Animals with previous cocaine experience exhibited significantly greater locomotor activity and number of rearings. There was no difference between groups in cocaine levels in various brain regions, plasma, or liver. Brain cocaine content in various regions was significantly correlated, though heterogeneously distributed within the various regions. The highest cocaine levels were found in hippocampus, striatum, thalamus/hypothalamus, and cortex. These results provide further evidence that behavioral sensitization is not the result of cocaine redistribution following repeated administration.