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Initial deficit and recovery of function after MDMA preexposure in rats

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Abstract

Rationale

3,4-methylenedioxymethamphetamine (MDMA) exposure was reported to result in deficits in serotonergic neurotransmission with concomitant behavioral suppression and tolerance to MDMA. Some data have also suggested that the neurochemical deficits recover over time, raising the question as to whether behavioral suppression would show a similar recovery.

Objectives

The possibility of recovery of behavioral deficits was examined in the present study. Rats were administered an MDMA pretreatment regimen that was shown to produce numerous serotonergic deficits and behavioral suppression 2 weeks thereafter. The full expression of MDMA-produced hyperactivity was dependent upon serotonergic integrity, therefore, the present study aimed to determine whether MDMA pretreated rats were tolerant to MDMA 2 weeks after exposure. Further, because serotonergic deficits have shown recovery over time, similar behavioral tests were conducted at a later time point to determine whether functional recovery was evident.

Methods

MDMA-produced hyperactivity was measured at different withdrawal periods (2 and 12 weeks) to determine initial effects and the possibility of recovery of function.

Results

In saline-pretreated control rats, +/−MDMA (0.0–10.0 mg/kg) produced a dose-dependent increase in locomotor activity. Rats that had received prior exposure to MDMA (4×10 mg/kg MDMA injections administered at 2 h intervals) demonstrated tolerance when the activity was measured 2 weeks after pretreatment. For these rats, there was a downward shift in the dose–effect curve for MDMA-produced hyperactivity. MDMA-produced hyperactivity in rats that were tested 12 weeks after pretreatment was, however, comparable to controls, suggesting recovery of function.

Conclusion

These data are consistent with the idea that high dose MDMA exposure produces neuroadaptations that exhibit recovery with extended abstinence from the drug.

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Acknowledgements

Funding was provided by the Lottery Health Foundation, Neurological Foundation of New Zealand, and the School of Psychology at Victoria University in Wellington, NZ. The authors greatly acknowledge the technical assistance of Richard Moore, Evangeline Daniela, and David Gittings.

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  1. Victoria University of Wellington, School of Psychology, P.O. Box 600, Wellington, New Zealand

    K. A. Brennan & S. Schenk

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Brennan, K.A., Schenk, S. Initial deficit and recovery of function after MDMA preexposure in rats. Psychopharmacology 184, 239–246 (2006). https://doi.org/10.1007/s00213-005-0278-y

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