ArticlesThe Anxiogenic-Like and Anxiolytic-Like Effects of MDMA on Mice in the Elevated Plus-Maze: A Comparison With Amphetamine
Section snippets
Subjects
Eight to 11-week-old, male Quackenbush Swiss (QS) mice (an outbred strain obtained from the University of Sydney SPF facility, Little Bay, Australia) were used. They were group (n = 10) housed in plastic cages with free access to water and standard laboratory chow. The animal house was maintained at 21 ± 1°C and a 12 L:12 D cycle. The experiments were conducted from 1030–1630 h, and the testing order for different treatments were counterbalanced to limit the time effect. Each animal was used
Results
The effects of MDMA on responses to the plus maze are depicted in Fig. 1. In a dose-related fashion, the actions of MDMA varied from anxiogenicity to anxiolysis with increasing dose. At the dose of 1 mg/kg, MDMA did not have any significant effect on all measures. When the dose was increased to 4 mg/kg, the drug markedly reduced % open entries (p < 0.01) and significantly increased enclosed entries (p < 0.05), indicating an anxiogenic-like and an stimulant effect, respectively. At the dose of
Discussion
The present study clearly demonstrates dose-dependent, “paradoxical” effects of MDMA in the elevated plus-maze test. These effects can be summarized as follows: a 1-mg/kg dose was inactive, 4 mg/kg exerted an anxiogenic-like action as well as a hyperactive effect, 12 mg/kg seemed to be a transient dose level between anxiogenicity and anxiolysis, and 20 mg/kg gave rise to anxiolysis. The results suggest that MDMA possesses dual pharmacological properties, capable of activating both excitatory
Acknowledgements
This work was supported by Polychip Pharmaceuticals Pty. Ltd, and an Australian Research Council Collaborative Research Grant to G. A. R. J. and P. M. B. The authors thank National Institute on Drug Abuse, USA, for donation of MDMA, and Keith Rippon and Norm Oetsch for their excellent technical assistance.
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