Segat Hecson J, Metz Vinícia G, Rosa Higor Z, Dias Verônica T, Barcelos Raquel C S, Dolci Geisa S, Burger Marilise E
Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil.
Pós-Graduação em Farmacologia, UFSM, RS, Brazil.
Neurosci Lett. 2019 Jan 18;690:138-144. doi: 10.1016/j.neulet.2018.10.007. Epub 2018 Oct 5.
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 (10mg/mL) of AMPH was used, consisting of the AMPH isotherapic (AMPH-ISO), which can be used as a replacement therapy to treat AMPH addiction.
To verify the influence of AMPH-ISO on toxicological aspects of AMPH addiction.
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.
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.
This study shows that an ultra-high dilution of AMPH may be a useful alternative which can contribute with AMPH addiction treatment.
安非他命（AMPH）与成瘾、类似焦虑行为以及长期使用后的记忆损伤有关。在当前实验中，使用了安非他命的超高稀释液（10mg/mL），即安非他命等温液（AMPH-ISO），其可作为治疗安非他命成瘾的替代疗法。
验证AMPH-ISO对安非他命成瘾毒理学方面的影响。
大鼠在条件性位置偏爱（CPP）范式中接受d，l-安非他命（4.0mg/kg，腹腔注射），持续8天。然后，每个实验组（安非他命组或生理盐水组）的一半大鼠接受AMPH-ISO/赋形剂（每只大鼠0.2mL，每天一次），持续14天。在第15天，动物在单次注射安非他命（2.0mg/kg）后，在CPP范式中重新评估（以验证复发行为）。随后，对类似焦虑行为进行量化，接着在前额叶皮质进行体外分析。
AMPH-ISO可预防与安非他命共同处理的动物出现类似安非他命的复发行为，并降低其本身的类似焦虑行为。分子分析表明，AMPH-ISO调节了多巴胺能靶点（多巴胺转运体、酪氨酸羟化酶和D1-R），安非他命可增加这些靶点的免疫反应性。此外，AMPH-ISO增加了过氧化氢酶活性和NPSH水平，并降低了前额叶皮质中的脂质过氧化和蛋白质羰基水平。
本研究表明，安非他命的超高稀释液可能是一种有用的替代方法，有助于安非他命成瘾的治疗。
