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Repeated administration of the 5-HT1B/1A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT1A and 5-HT1B receptor mechanisms

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Abstract

Rationale

3,4 Methylenedioxymethamphetamine (MDMA) preferentially stimulates the release of serotonin (5-HT) that subsequently produces behavioral responses by activation of post-synaptic receptor mechanisms. The 5-HT1A and 5-HT1B receptors are both well localized to regulate dopamine (DA) release, and have been implicated in modulating the reinforcing effects of many drugs of abuse, but a role in acquisition of self-administration has not been determined.

Objectives

This study was designed to determine the effect of pharmacological manipulation of 5-HT1A and 5-HT1B receptor mechanisms on the acquisition of MDMA self-administration.

Methods

The 5-HT1B/1A receptor agonist, RU 24969 (0.0 or 3.0 mg/kg, bid), was administered for 3 days in order to down-regulate both 5-HT1A and 5-HT1B receptors. Following the pretreatment phase, latency to acquisition of MDMA self-administration was measured.

Results

Repeated administration of RU 24969 significantly decreased the latency to acquisition and increased the proportion of animals that acquired MDMA self-administration. Dose-effect curves for the 5-HT1A-mediated hyperactivity produced by the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT1B-mediated adipsic response produced by RU 24969 were shifted rightward, suggesting a desensitization of 5-HT1A and 5-HT1B receptor mechanisms.

Conclusions

These data suggest that the initial reinforcing effects of MDMA are modulated by 5-HT1A and/or 5-HT1B receptor mechanisms. The potential impact of these changes on the DAergic response relevant to self-administration and a possible role in conditioned reinforcement pertaining to acquisition of self-administration are discussed.

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

    Dane Aronsen, Natasha Bukholt & Susan Schenk

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  1. Dane Aronsen
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  2. Natasha Bukholt
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  3. Susan Schenk
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Correspondence to Susan Schenk.

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All procedures were approved by the Victoria University of Wellington Animal Ethics Committee.

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Aronsen, D., Bukholt, N. & Schenk, S. Repeated administration of the 5-HT1B/1A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT1A and 5-HT1B receptor mechanisms. Psychopharmacology 233, 1339–1347 (2016). https://doi.org/10.1007/s00213-016-4225-x

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