Malin D H, Lake J R, Short P E, Blossman J B, Lawless B A, Schopen C K, Sailer E E, Burgess K, Wilson O B
University of Houston-Clear Lake, TX 77058, USA.
Pharmacol Biochem Behav. 1996 Jul;54(3):581-5. doi: 10.1016/0091-3057(95)02279-1.
In a recently introduced rodent model of nicotine abstinence syndrome the observed behavioral signs closely resembled those typical of rat opiate abstinence syndrome. Nicotine-induced release of endogenous opioids may contribute to nicotine dependence; morphine potently reverses nicotine abstinence signs, while naloxone precipitates abstinence signs and prevents nicotine from alleviating them. Considerable evidence suggests that neuropeptide FF, an endogenous antiopiate peptide, contributes to opiate dependence. Third ventricle injection of neuropeptide FF precipitates abstinence syndrome in morphine-dependent rats, as does SC injection of its lipophilic analogs, dansyl-PQRFamide and dansyl-RFamide. Might NPFF also play a role in nicotine dependence? In the present study, SC injection of 15 or 25 mg/kg dansyl-RFamide or vehicle alone dose dependently precipitated an abstinence syndrome in nicotine-dependent rats. There was a significant, p < 0.01, positive linear trend of abstinence signs as a function of dose. Categories of abstinence signs had the same rank ordering by frequency as observed in spontaneous nicotine abstinence. Injection of 25 mg/kg dansyl-RFamide SC had no significant effect in nondependent rats.
在最近引入的尼古丁戒断综合征啮齿动物模型中,观察到的行为体征与大鼠阿片类药物戒断综合征的典型体征极为相似。尼古丁诱导内源性阿片类物质的释放可能导致尼古丁依赖;吗啡能有效逆转尼古丁戒断体征,而纳洛酮则会引发戒断体征,并阻止尼古丁缓解这些体征。大量证据表明,神经肽FF(一种内源性抗阿片肽)与阿片类药物依赖有关。向第三脑室注射神经肽FF会使吗啡依赖的大鼠出现戒断综合征,皮下注射其亲脂性类似物丹磺酰-PQRF酰胺和丹磺酰-RF酰胺也会出现这种情况。神经肽FF在尼古丁依赖中是否也起作用呢?在本研究中,皮下注射15或25mg/kg丹磺酰-RF酰胺或单独注射赋形剂会使尼古丁依赖的大鼠出现剂量依赖性的戒断综合征。戒断体征呈显著的(p<0.01)正线性趋势,与剂量相关。戒断体征的类别按频率排列与自发尼古丁戒断时观察到的相同。皮下注射25mg/kg丹磺酰-RF酰胺对非依赖性大鼠无显著影响。