Hernandez Giovanni, Haines Eric, Shizgal Peter
Groupe de recherche en neurobiologie comportementale/Center for Studies in Behavioural Neurobiology (GRNC/CSBN), Concordia University, Montréal, Québec, Canada.
J Neurosci Methods. 2008 Oct 30;175(1):79-87. doi: 10.1016/j.jneumeth.2008.08.005. Epub 2008 Aug 12.
Subcutaneous administration of cocaine yields a longer duration of action than administration via the intraperitoneal or intravenous routes. However, cocaine is a powerful vasoconstrictor, and thus injection of this drug at a single subcutaneous locus entails significant risk of necrotic skin lesions. This paper introduces a new method for subcutaneous administration of cocaine that reduces the probability of dermonecrosis by dispersing the drug under a large area of skin. Two experiments were conducted to evaluate the new method. In the first, changes in dopamine tone in the nucleus accumbens were measured by means of microdialysis during prolonged subcutaneous infusions of cocaine. The dopamine concentration attained a fairly stable, elevated level, suggesting that absorption, distribution, and excretion of the drug approached steady state. In a second experiment, performance for rewarding electrical stimulation was measured during repeated prolonged infusions of cocaine. The pulse frequency required to sustain responding was decreased by the drug, in a manner that was stable both within and across test sessions. Thus, the new method is appropriate for studies requiring stable neurochemical and behavioral conditions during repeated long test sessions, high rates of drug delivery and alternation between administration of the drug and the vehicle.
与通过腹腔内或静脉内途径给药相比，皮下注射可卡因的作用持续时间更长。然而，可卡因是一种强效血管收缩剂，因此在单一皮下部位注射这种药物会带来皮肤坏死性病变的重大风险。本文介绍了一种皮下注射可卡因的新方法，该方法通过将药物分散在大面积皮肤下降低了皮肤坏死的可能性。进行了两项实验来评估这种新方法。在第一项实验中，在长时间皮下输注可卡因期间，通过微透析测量伏隔核中多巴胺水平的变化。多巴胺浓度达到了相当稳定的升高水平，表明药物的吸收、分布和排泄接近稳态。在第二项实验中，在重复长时间输注可卡因期间测量对奖励性电刺激的行为表现。维持反应所需的脉冲频率因药物而降低，在测试期间内和测试期间之间都是稳定的。因此，这种新方法适用于在重复的长时间测试期间需要稳定的神经化学和行为条件、高药物递送率以及在药物和载体给药之间交替的研究。
