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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.
Psychopharmacology (Berl). 2016 Apr; 233(8):1339-47.P

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.

Authors+Show Affiliations

School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand. Susan.schenk@vuw.ac.nz.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26856853

Citation

Aronsen, Dane, et al. "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, vol. 233, no. 8, 2016, pp. 1339-47.
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 (Berl). 2016;233(8):1339-47.
Aronsen, D., Bukholt, N., & Schenk, S. (2016). 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(8), 1339-47. https://doi.org/10.1007/s00213-016-4225-x
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 (Berl). 2016;233(8):1339-47. PubMed PMID: 26856853.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Aronsen,Dane, AU - Bukholt,Natasha, AU - Schenk,Susan, Y1 - 2016/02/09/ PY - 2015/11/04/received PY - 2016/01/27/accepted PY - 2016/2/10/entrez PY - 2016/2/10/pubmed PY - 2016/12/15/medline KW - 5-HT1A KW - 5-HT1B KW - Acquisition KW - Dopamine KW - MDMA KW - RU 24969 KW - Self-administration KW - Serotonin SP - 1339 EP - 47 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 233 IS - 8 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/26856853/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_ L2 - https://dx.doi.org/10.1007/s00213-016-4225-x DB - PRIME DP - Unbound Medicine ER -