Articles
The Anxiogenic-Like and Anxiolytic-Like Effects of MDMA on Mice in the Elevated Plus-Maze: A Comparison With Amphetamine

https://doi.org/10.1016/S0091-3057(98)00191-9Get rights and content

Abstract

Many abused substances have been found to possess anxiogenic-like or/and anxiolytic-like properties. Discrepancies about the effects of MDMA, one of the most popular recreational drugs in recent years, on anxiety have been seen in the literature, and almost all of the data in this respect were derived from retrospective studies. The present study was thus designed to examine the drug’s actions by using an animal model of anxiety, the elevated plus-maze test in male mice. Intraperitoneal MDMA at 1 mg/kg was ineffective, at 4 mg/kg decreased the percent of open arm entries (p < 0.01), and increased enclosed entries (p < 0.05), at 12 mg/kg had no significant effect, and at 20 mg/kg induced an increase of percent of open time (p < 0.01). As control drugs, amphetamine (0.5–4 mg/kg, IP) produced a dose-dependent, anxiogenic-like effect and diazepam (1 mg/kg, IP) induced an anxiolytic-like effect in the test. The results indicate that MDMA has anxiogenic-like properties at lower doses and anxiolytic-like at higher doses. The effects of MDMA and amphetamine on the mouse’s responses to the plus-maze are compared. These findings provide a possible explanation for the controversies over MDMA’s effects on anxiety in the literature.

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.

References (39)

  • M.D. Schechter

    Effect of MDMA neurotoxicity upon its conditioned place preference and discrimination

    Pharmacol. Biochem. Behav.

    (1991)
  • F. Schifano

    Chronic atypical psychosis associated with MDMA (“ecstasy”) abuse

    Lancet

    (1991)
  • P. Simon et al.

    Anxiogenic-like effects induced by stimulation of dopamine receptors

    Pharmacol. Biochem. Behav.

    (1993)
  • S. Williamson et al.

    Adverse effects of stimulant drugs in a community sample of drug users

    Drug Alcohol. Depend.

    (1997)
  • N. Andrews et al.

    Evidence that the median raphe nucleus–dorsal hippocampal pathway mediates diazepam withdrawal-induced anxiety

    Psychopharmacology (Berlin)

    (1997)
  • G. Battaglia et al.

    MDMA effects in brainPharmacologic profile and evidence of neurotoxicity from neurochemical and autoradiographic studies

  • M.P. Bird et al.

    Evidence for dopaminergic but not serotonergic mediation of the threshold lowering effects of MDMA on reward brain stimulation

    Soc. Neurosci. Abstr.

    (1987)
  • C.W. Callaway et al.

    Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats

    J. Pharmacol. Exp. Ther.

    (1990)
  • G.R. Dawson et al.

    Evidence that the anxiolytic-like effects of chlordiazepoxide on the elevated plus maze are confounded by increases in locomotor activity

    Psychopharmacology (Berlin)

    (1995)
  • Cited by (0)

    View full text