BEHAVIORAL-RESPONSES TO LOW-DOSES OF COCAINE ARE AFFECTED BY GENETICSAND EXPERIMENTAL HISTORY

We recently conducted a set of two experiments to investigate the poss ible co-operation between genetics and exposure to novelty on the puta tive 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, ex ploration, stereotypy and wall-seeking in an automated activity monito r. Testing occurred on two consecutive days, with subjects receiving a n IP injection of saline on day one, and one dose of cocaine on day 2 (S-C). Immediately following injection, subjects were placed into auto mated activity monitors, where four behaviors were recorded; total dis tance, 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 mi ce. Experiment two was designed to determine if the observed decrease in locomotor activity was the result of low-dose cocaine or pre-exposu re to the test procedure and apparatus. All conditions and procedures were identical to those in experiment one, with the exception of the i njection 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). Ad ditionally, a group of subjects receiving saline on both days (S-S) se rved as the control. In contrast to experiment one results, cocaine pr oduced locomotor activation. Furthermore, significant sex and strain d ifferences were found in both experiments. The results of our experime nts suggest that the behavioral effects of low doses of cocaine are ma rkedly influenced by both the genetic constitution of the experimental animal and by familiarity with the test apparatus.