Anxiogenic action of acute but not repeated cocaine administration in handling-habituated mice in the plus-maze test.

The present study was designed to determine the putative anxiogenic effects of cocaine on the performance of mice in the elevated plus-maze test of anxiety. Male Swiss mice, weighing about 30 g, treated repeatedly with saline for 8 days and challenged with a single injection of cocaine 10 mg/kg, ip, 1 ml/100 g, on day 10, showed a clear reduction in the relative number (%) of entries and time spent on the open arms of the maze (30.5 +/- 4.5 and 29.4 +/- 5.0 vs 47.1 +/- 6.2 and 46.7 +/- 9.4, for the controls, respectively, N = 7-8 animals). These data suggest an anxiogenic action of cocaine. However, acute treatment with cocaine (5-20 mg/kg, ip) of naive mice and repeated administration of cocaine (10 mg/kg) for 8 days failed to alter the indices of anxiety in the test. These findings suggest that the emotional changes induced by the handling procedures for 8 days may be related to the occurrence of anxiogenic responses to cocaine by mice.