Zaniewska Magdalena, McCreary Andrew C, Sezer Gulay, Przegaliński Edmund, Filip Małgorzata
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2008 Sep-Oct;60(5):645-54.
Agmatine [2-(4-aminobutyl)guanidine], is a novel endogenous ligand at alpha2-adrenoceptors, imidazoline and N-methyl-D-asparate receptors, as well as a nitric oxide synthase inhibitor. The present study tested whether agmatine (5-40 mg/kg, sc) modulated the locomotor, sensitizing, and discriminative stimulus effects of nicotine in male Wistar rats. Agmatine (10-40 mg/kg) affected neither the basal locomotor activity, nor the nicotine (0.4 mg/kg, sc)-evoked hyperactivation. A challenge with saline or nicotine (0.4 mg/kg, sc) on day 10 to rats treated repeatedly (for 5 days) with nicotine (0.4 mg/kg, sc; and exposed to experimental chambers), resulted in the expression of nicotine-evoked conditioned hyperlocomotor response or behavioral sensitization. Given on day 10, agmatine at a dose of 40 mg/kg (but not 20 mg/kg) attenuated nicotine-induced conditioned hyperactivity. However, when this dose was administered to the nicotine-sensitized rats, agmatine failed to alter the effect of the challenge dose of nicotine. In rats trained to discriminate nicotine (0.4 mg/kg, sc) from saline in a two-lever water-reinforced fixed ratio 10 task, agmatine (20 or 40 mg/kg) did not substitute for the training dose of nicotine. In combination studies, pretreatment with agmatine (5-40 mg/kg) did not affect the nicotine (0.4 mg/kg) discrimination and the fixed dose of agmatine (20 mg/kg) did not change the effects of the lower doses of nicotine (0.05-0.2 mg/kg). Our pharmacological analyses indicate that agmatine does not affect the locomotor, sensitizing, or subjective effects of nicotine. However, these data do show an inhibitory effect of agmatine over the expression of nicotine-induced conditioned hyperlocomotion.
胍丁胺[2-(4-氨基丁基)胍]是一种新型内源性配体，作用于α2-肾上腺素能受体、咪唑啉受体和N-甲基-D-天冬氨酸受体，同时也是一种一氧化氮合酶抑制剂。本研究检测了胍丁胺(5-40mg/kg，皮下注射)是否能调节雄性Wistar大鼠中尼古丁的运动、致敏和辨别刺激效应。胍丁胺(10-40mg/kg)既不影响基础运动活性，也不影响尼古丁(0.4mg/kg，皮下注射)诱发的运动亢进。在第10天，对反复(连续5天)接受尼古丁(0.4mg/kg，皮下注射)处理并置于实验箱中的大鼠，用生理盐水或尼古丁(0.4mg/kg，皮下注射)进行激发，可导致尼古丁诱发的条件性运动亢进反应或行为致敏的表达。在第10天给予40mg/kg(而非20mg/kg)的胍丁胺可减弱尼古丁诱导的条件性多动。然而，当将此剂量给予尼古丁致敏大鼠时，胍丁胺未能改变激发剂量尼古丁的效应。在经过训练能在双杠杆水强化固定比率10任务中区分尼古丁(0.4mg/kg，皮下注射)和生理盐水的大鼠中，胍丁胺(20或40mg/kg)不能替代训练剂量的尼古丁。在联合研究中，用胍丁胺(5-40mg/kg)预处理不影响尼古丁(0.4mg/kg)辨别，固定剂量的胍丁胺(20mg/kg)也不改变较低剂量尼古丁(0.05-0.2mg/kg)的效应。我们的药理学分析表明，胍丁胺不影响尼古丁的运动、致敏或主观效应。然而，这些数据确实显示了胍丁胺对尼古丁诱导的条件性运动亢进表达的抑制作用。
