Abstract
Different neurotransmitter brain systems have been implicated in the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA), including dopamine or serotonin. Serotonin selective reuptake inhibitors (SSRI) are a commonly prescribed therapy for psychiatric disorders, and the SSRI fluoxetine is recommended for MDMA users due to its neuroprotective effect against MDMAinduced neurotoxicity. In the present work, we employed the conditioned place preference (CPP) paradigm to study how the inhibition of serotonin reuptake with fluoxetine affected the rewarding and reinstating effects of MDMA in adolescent male mice. Firstly, we evaluated the motivational effects of fluoxetine (1 and 10 mg/kg), administered alone or with a sub-threshold dose of MDMA (1.25 mg/kg). In a second experiment we evaluated the effects of a pretreatment with fluoxetine (1 and 10 mg/kg) on the subsequent acquisition of a CPP induced by MDMA (1.25 mg/kg). The effects of a priming dose of fluoxetine (1 and 10 mg/kg), MDMA (5 or 1.25 mg/kg) or both drugs together on the reinstatement of a previously extinguished CPP induced by MDMA (10 mg/kg) were studied in a third experiment. Fluoxetine did not induce motivational effects but did increase the rewarding effects of a sub-threshold dose of MDMA, and pretreatment with the high dose of fluoxetine had the same effect. Fluoxetine did not induce cross-reinstatement of the MDMA CPP, but the combination of an ineffective priming dose of MDMA and the highest dose of fluoxetine did induce reinstatement of CPP. Neurochemical experiments demonstrated alterations in monoamine levels of MDMA treated mice produced by fluoxetine. As a whole, these results show that the inhibition of serotonin reuptake potentiates the acquisition and reinstatement of MDMA-induced CPP and supports a role for serotonin in MDMA-induced reward.
Keywords: MDMA, fluoxetine, conditioned place preference, reinstatement, mice.
Current Pharmaceutical Design
Title:Neurochemical Substrates of MDMA Reward: Effects of the Inhibition of Serotonin Reuptake on the Acquisition and Reinstatement of MDMA-induced CPP
Volume: 19 Issue: 40
Author(s): C. Roger-Sánchez, M. A. Aguilar, C. Manzanedo, J. Miñarro and M. Rodríguez-Arias
Affiliation:
Keywords: MDMA, fluoxetine, conditioned place preference, reinstatement, mice.
Abstract: Different neurotransmitter brain systems have been implicated in the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA), including dopamine or serotonin. Serotonin selective reuptake inhibitors (SSRI) are a commonly prescribed therapy for psychiatric disorders, and the SSRI fluoxetine is recommended for MDMA users due to its neuroprotective effect against MDMAinduced neurotoxicity. In the present work, we employed the conditioned place preference (CPP) paradigm to study how the inhibition of serotonin reuptake with fluoxetine affected the rewarding and reinstating effects of MDMA in adolescent male mice. Firstly, we evaluated the motivational effects of fluoxetine (1 and 10 mg/kg), administered alone or with a sub-threshold dose of MDMA (1.25 mg/kg). In a second experiment we evaluated the effects of a pretreatment with fluoxetine (1 and 10 mg/kg) on the subsequent acquisition of a CPP induced by MDMA (1.25 mg/kg). The effects of a priming dose of fluoxetine (1 and 10 mg/kg), MDMA (5 or 1.25 mg/kg) or both drugs together on the reinstatement of a previously extinguished CPP induced by MDMA (10 mg/kg) were studied in a third experiment. Fluoxetine did not induce motivational effects but did increase the rewarding effects of a sub-threshold dose of MDMA, and pretreatment with the high dose of fluoxetine had the same effect. Fluoxetine did not induce cross-reinstatement of the MDMA CPP, but the combination of an ineffective priming dose of MDMA and the highest dose of fluoxetine did induce reinstatement of CPP. Neurochemical experiments demonstrated alterations in monoamine levels of MDMA treated mice produced by fluoxetine. As a whole, these results show that the inhibition of serotonin reuptake potentiates the acquisition and reinstatement of MDMA-induced CPP and supports a role for serotonin in MDMA-induced reward.
Export Options
About this article
Cite this article as:
Roger-Sánchez C., Aguilar A. M., Manzanedo C., Miñarro J. and Rodríguez-Arias M., Neurochemical Substrates of MDMA Reward: Effects of the Inhibition of Serotonin Reuptake on the Acquisition and Reinstatement of MDMA-induced CPP, Current Pharmaceutical Design 2013; 19 (40) . https://dx.doi.org/10.2174/138161281940131209143632
DOI https://dx.doi.org/10.2174/138161281940131209143632 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
VIP in Neurological Diseases: More Than A Neuropeptide
Endocrine, Metabolic & Immune Disorders - Drug Targets Mitochondriotropic Cationic Vesicles A Strategy Towards Mitochondrial Gene Therapy
Current Pharmaceutical Biotechnology Antioxidant Therapy in Diabetic Complications: What is New?
Current Vascular Pharmacology Factors Affecting Sexual Transmission of HIV-1: Current Evidence and Implications for Prevention
Current HIV Research The Potentials of Selected Therapeutic Targets for Inflammation: A Snapshot
Recent Patents on Inflammation & Allergy Drug Discovery miRNAs Highlights in Stem and Cancer Cells
Mini-Reviews in Medicinal Chemistry Aspartic Proteases of Human Pathogenic Fungi are Prospective Targets for the Generation of Novel and Effective Antifungal Inhibitors
Current Enzyme Inhibition Rab GTPases, Membrane Trafficking and Diseases
Current Drug Targets ADAM10 as a Therapeutic Target for Cancer and Inflammation
Current Pharmaceutical Design Proteomics Approaches to Understand Linkage Between Alzheimer’s Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Contrasting Roles of the Galectin-3 in the Schizophrenia Onset, Clinical Presentation, and Somatic Comorbidity
Current Topics in Medicinal Chemistry Combinational Approaches Targeting Neurodegeneration, Oxidative Stress, and Inflammation in the Treatment of Diabetic Retinopathy
Current Drug Targets Therapeutic Advances in the Treatment of Alzheimer's Disease: Present and Future
Current Drug Therapy Visceral and Subcutaneous Adiposity: Are Both Potential Therapeutic Targets for Tackling the Metabolic Syndrome?
Current Pharmaceutical Design Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiac Structural and Electrical Remodeling: From Myocardial Cytology to Cardiodiabetology
Current Vascular Pharmacology Ontogeny of Hepatic Glucuronidation; Methods and Results
Current Drug Metabolism Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design γ-Secretase as a Therapeutic Target for the Treatment of Alzheimers Disease
Current Pharmaceutical Design Amyloid-Degrading Enzymes as Therapeutic Targets in Alzheimers Disease
Current Alzheimer Research