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MDMA self-administration fails to alter the behavioral response to 5-HT1A and 5-HT1B agonists

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Abstract

Rationale

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT1A and 5-HT1B receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA.

Objectives

This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT1A agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT1B/1A agonist, RU 24969.

Methods

Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20–58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03–1.0 mg/kg) or the adipsic response to RU 24969 (0.3–3.0 mg/kg) were assessed.

Results

8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration.

Conclusions

Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT1A or 5-HT1B receptor mechanisms.

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The authors gratefully acknowledge the technical support of Michael Roberts.

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

    Dane Aronsen & Susan Schenk

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  1. Dane Aronsen
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Correspondence to Susan Schenk.

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Aronsen, D., Schenk, S. MDMA self-administration fails to alter the behavioral response to 5-HT1A and 5-HT1B agonists. Psychopharmacology 233, 1323–1330 (2016). https://doi.org/10.1007/s00213-016-4226-9

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