Sudakov S K, Bogdanova N G
P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia.
Bull Exp Biol Med. 2016 Oct;161(6):743-745. doi: 10.1007/s10517-016-3499-7. Epub 2016 Oct 26.
The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.
该研究考察了外周（胃内）给予ICI-204,448（一种胃κ-阿片受体激动剂）对尼古丁依赖大鼠在尼古丁戒断阶段咖啡因的精神刺激作用和抗焦虑作用的影响。在这些大鼠中，咖啡因（10毫克/千克）的作用发生了改变。与在无尼古丁依赖的正常大鼠中咖啡因诱导的致焦虑作用相反，在尼古丁依赖大鼠中，咖啡因产生了抗焦虑作用，并伴有明显的运动活动刺激。在尼古丁戒断期间，尼古丁依赖大鼠对尼古丁表现出增强的敏感性。胃内给予κ-阿片受体激动剂ICI-204,448使咖啡因在尼古丁依赖大鼠中的作用恢复正常。我们之前已经证明，外周κ-阿片受体的激活抑制了中枢κ-阿片活性，并消除了尼古丁依赖大鼠尼古丁戒断综合征的表现，例如代谢激活、运动活动刺激和食物消耗增加。反过来，中枢κ-阿片结构的抑制激活了脑腺苷系统，这可能会减弱咖啡因在尼古丁依赖大鼠中诱导的作用。
