Behavioral responses to low doses of cocaine are affected by genetics and experimental history

We recently conducted a set of two experiments to investigate the possible co-operation between genetics and exposure to novelty on the putative locomotor inhibiting effects of low doses of cocaine in male and female C57BL/6 and DBA/2 mice. Experiment one examined the effects of three low doses of cocaine (0.1, 0.5, and 1.0 mg/kg) on locomotion, exploration, stereotypy and wall-seeking in an automated activity monitor. Testing occurred on two consecutive days, with subjects receiving an IP injection of saline on day one, and one dose of cocaine on day 2 (S-C). Immediately following injection, subjects were placed into automated activity monitors, where four behaviors were recorded; total distance, nosepokes, stereotypy and margin time. Using this S-C injection regimen, we found significant decreases in measures of total distance and stereotypy when compared to saline in both male and female C57 mice. Experiment two was designed to determine if the observed decrease in locomotor activity was the result of low-dose cocaine or pre-exposure to the test procedure and apparatus. All conditions and procedures were identical to those in experiment one, with the exception of the injection regimen. In this experiment, we injected all subjects IP with 0.1 mg/kg cocaine on day one, followed by saline on day two (C-S). Additionally, a group of subjects receiving saline on both days (S-S) served as the control. In contrast to experiment one results, cocaine produced locomotor activation. Furthermore, significant sex and strain differences were found in both experiments. The results of our experiments suggest that the behavioral effects of low doses of cocaine are markedly influenced by both the genetic constitution of the experimental animal and by familiarity with the test apparatus.