Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos, SP, Brazil.
Instituto de Ciências do Mar, Universidade Federal de São Paulo (UNIFESP), Santos, SP, Brazil.
Exp Brain Res. 2021 Apr;239(4):1179-1191. doi: 10.1007/s00221-020-06031-2. Epub 2021 Feb 10.
Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine.
快克可卡因是可卡因的晶体形式，通过向可卡因碱糊中加入碳酸氢钠制成。巴西是世界上最大的快克可卡因消费国。快克可卡因的使用者表现出重要的生理和行为改变，包括神经精神症状，如与焦虑相关的症状。然而，此前很少有临床前研究来了解快克可卡因的神经生物学效应。本研究的目的是在焦虑/惊恐的动物模型——高架 T 迷宫（ETM）中，研究大鼠亚慢性（5 天，IP）给予快克可卡因的影响。ETM 模型允许测量两种行为防御反应，回避和逃避，在临床术语中，分别与广泛性焦虑症和惊恐障碍相关，这是两种伴随物质使用障碍的主要精神疾病。在 ETM 模型后，立即在开阔场中测试动物以评估运动活动。Delta FosB 蛋白免疫反应性分析用于绘制快克可卡因暴露激活的区域图。结果表明，快克可卡因处理选择性地改变了 ETM 测试中大鼠的逃避行为，诱导了惊恐发作（18mg/kg IP）或类似惊恐发作的效应（25 和 36mg/kg IP）。这些效应随后伴随着惊恐调节脑区功能的改变，即导水管周围灰质以及中脑导水管周围灰质背侧区和背侧中缝核的外侧翼。36mg/kg 快克可卡因处理还增加了运动活动。这是在焦虑/惊恐的啮齿动物模型中首次用快克可卡因进行的观察，有助于更好地了解快克可卡因的行为和神经生物学效应。
