Substitution therapy with amphetamine-isotherapic attenuates amphetamine toxicological aspects of addiction
| Autor: | H.Z. Rosa, H.J. Segat, Raquel Cristine Silva Barcelos, Verônica Tironi Dias, Vinícia Garzella Metz, Marilise Escobar Burger, G.S. Dolci |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Tyrosine 3-Monooxygenase media_common.quotation_subject Conditioning Classical Prefrontal Cortex Pharmacology Protein Carbonylation 03 medical and health sciences 0302 clinical medicine Animals Medicine Sulfhydryl Compounds Maze Learning Amphetamine Prefrontal cortex media_common Dopamine transporter Dopamine Plasma Membrane Transport Proteins Dose-Response Relationship Drug biology Tyrosine hydroxylase business.industry Receptors Dopamine D1 General Neuroscience Addiction Dopaminergic Catalase Conditioned place preference Rats Cortex (botany) Behavior Addictive 030104 developmental biology biology.protein Lipid Peroxidation business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience Letters. 690:138-144 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2018.10.007 |
| Popis: | Introduction amphetamine (AMPH) is related to development of addiction, anxiety-like behaviors and impairments of memory after chronic use. In the current experiment, an ultra-high dilution (10−24mg/mL) of AMPH was used, consisting of the AMPH isotherapic (AMPH-ISO), which can be used as a replacement therapy to treat AMPH addiction. Aim To verify the influence of AMPH-ISO on toxicological aspects of AMPH addiction. Methods Rats received d,l-AMPH (4.0 mg/kg, i.p.) in the conditioned place preference (CPP) paradigm (8 days). Then, half of each experimental group (AMPH or saline) received AMPH-ISO/vehicle (0.2 mL per rat, once a day), for fourteen days. On the fifteenth day, animals were re-assessed in the CPP paradigm (to verify relapse behaviors) after a single dose of AMPH (2.0 mg/kg). Subsequently, anxiety-like behaviors were quantified, followed by ex vivo assays in the pre-frontal cortex. Results AMPH-ISO prevented relapse-like behavior of AMPH and reduced anxiety-like behavior per se in animals co-treated with AMPH. Molecular analysis evidenced that AMPH-ISO modulated dopaminergic targets (dopamine transporter, tyrosine hydroxylase and D1-R), whose immunoreactivity was increased by AMPH. Also, AMPH-ISO increased catalase activity and NPSH levels and reduced lipid peroxidation and protein carbonyl levels in the prefrontal cortex. Conclusion This study shows that an ultra-high dilution of AMPH may be a useful alternative which can contribute with AMPH addiction treatment. |
| Databáze: | OpenAIRE |
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