Cocaine actions, brain levels and receptors in selected lines of mice

The effects of cocaine (15 mg/kg IP) versus IP saline on open-field behaviors were evaluated using a crossover design in long-sleep (LS) and short-sleep (SS) mice. Under treatment order 1, mice received saline injection on day 1 followed 24 h later by cocaine (saline-cocaine, S-C). Under treatment order 2, animals received cocaine on day 1 and saline on day 2 (cocaine-saline, C-S). Immediately following injection, animals were placed into an automated open-field apparatus with behavioral samples taken at 5-min intervals for 30 min. The behaviors measured were distance traveled, stereotypy and time spent in proximity to the margins of the test apparatus (thigmotaxis). Cocaine increased locomotor activity in both lines of mice, with S-C producing more pronounced initial activation than C-S in LS mice. Compared to S-C, C-S also increased thigmotaxis, an effect more pronounced in SS mice. In a separate experiment, brain cocaine levels were measured in brains of adapted and nonadapted LS and SS mice 5 min following injection of 15 mg/kg cocaine. Regardless of order, SS mice had significantly higher brain cocaine levels than did LS mice. Mazindol and cocaine binding studies in the forebrain indicated higher B max values for both ligands in LS compared to SS mice. The results of this study indicate that genetically based differences in cocaine receptors as well astreatment order contribute to behavioral actions of cocaine.