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Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.
Psychopharmacology (Berl). 2017 Apr; 234(7):1155-1164.P

Abstract

RATIONALE

Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown.

OBJECTIVES

This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D2 receptor mechanisms.

METHODS

Rats received the selective D2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined.

RESULTS

Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration.

CONCLUSIONS

These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.

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. susan.schenk@vuw.ac.nz.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28188355

Citation

van de Wetering, Ross, and Susan Schenk. "Repeated MDMA Administration Increases MDMA-produced Locomotor Activity and Facilitates the Acquisition of MDMA Self-administration: Role of Dopamine D2 Receptor Mechanisms." Psychopharmacology, vol. 234, no. 7, 2017, pp. 1155-1164.
van de Wetering R, Schenk S. Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms. Psychopharmacology (Berl). 2017;234(7):1155-1164.
van de Wetering, R., & Schenk, S. (2017). Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms. Psychopharmacology, 234(7), 1155-1164. https://doi.org/10.1007/s00213-017-4554-4
van de Wetering R, Schenk S. Repeated MDMA Administration Increases MDMA-produced Locomotor Activity and Facilitates the Acquisition of MDMA Self-administration: Role of Dopamine D2 Receptor Mechanisms. Psychopharmacology (Berl). 2017;234(7):1155-1164. PubMed PMID: 28188355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms. AU - van de Wetering,Ross, AU - Schenk,Susan, Y1 - 2017/02/10/ PY - 2016/08/01/received PY - 2017/01/30/accepted PY - 2017/2/12/pubmed PY - 2017/12/2/medline PY - 2017/2/12/entrez KW - Dopamine receptor KW - Eticlopride KW - MDMA KW - Self-administration KW - Sensitization SP - 1155 EP - 1164 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 234 IS - 7 N2 - RATIONALE: Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown. OBJECTIVES: This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D2 receptor mechanisms. METHODS: Rats received the selective D2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined. RESULTS: Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration. CONCLUSIONS: These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/28188355/Repeated_MDMA_administration_increases_MDMA_produced_locomotor_activity_and_facilitates_the_acquisition_of_MDMA_self_administration:_role_of_dopamine_D2_receptor_mechanisms_ DB - PRIME DP - Unbound Medicine ER -