Shams Jamal, Sahraei Hedayat, Gholami Azam, Haeri-Rohani Ali, Alaf-Javadi Mahrooz, Sepehri Houri, Salimi Seyed H, Ghoshooni Hassan
Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Behav Pharmacol. 2006 Nov;17(7):629-35. doi: 10.1097/FBP.0b013e3280102d68.
In the present study, the effects of acute administration of nicotine, as well as nicotinic and muscarinic acetylcholine receptor antagonists, on the expression of morphine-induced conditioned place preference, have been investigated in male Swiss-Webster mice. Animals received different doses of morphine 5 days after surgical cannulation in the lateral ventricle. Subcutaneous injections of morphine (2-5 mg/kg) in mouse produced place preference in a dose-dependent manner. Furthermore, both intraperitoneal (0.0006-0.1 mg/kg) and intracerebroventricular (0.007-25 ng) nicotine administration significantly reduced the expression of morphine-induced place preference, in a dose-dependent manner. Nicotine, however, was effective over narrow ultra-low dose ranges (0.0012, 0.0025, 0.005 and 0.01 mg/kg; intraperitoneal) and (0.03, 0.1, 0.3 and 0.6 ng/mouse; intracerebroventricular). In addition, locomotor activity was reduced when higher doses of nicotine [both intraperitoneal (0.02, 0.03 and 0.1 mg/kg) and intracerebroventricular (10 and 24 ng/mouse)] were used. Nicotine alone, however, did not cause motivational effects. Intracerebroventricular injection of hexamethonium (0.03, 0.1 and 0.3 mug/mouse; 10 min before nicotine) diminished the effects of nicotine on morphine-induced conditioned place preference. This effect could neither be obtained by intraperitoneal administration of hexamethonium (1, 5 and 10 mg/kg; 30 min before nicotine), nor be reproduced after either intracerebroventricular or intraperitoneal injection of atropine (a muscarinic receptor antagonist). The antagonists, themselves, did not show any motivational effects when used alone and were unable to affect the expression of morphine-induced conditioned place preference. It appears that ultra-low doses of nicotine can reduce the expression of morphine-induced place preference, and that central nicotinic acetylcholine receptors play a role in this regard.
在本研究中，已在雄性瑞士-韦伯斯特小鼠中研究了急性给予尼古丁以及烟碱型和毒蕈碱型乙酰胆碱受体拮抗剂对吗啡诱导的条件性位置偏爱表达的影响。动物在侧脑室进行手术插管5天后接受不同剂量的吗啡。皮下注射吗啡（2-5mg/kg）可使小鼠产生剂量依赖性的位置偏爱。此外，腹腔注射（0.0006-0.1mg/kg）和脑室内注射（0.007-25ng）尼古丁均以剂量依赖性方式显著降低吗啡诱导的位置偏爱表达。然而，尼古丁仅在狭窄的超低剂量范围内有效（腹腔注射为0.0012、0.0025、0.005和0.01mg/kg；脑室内注射为0.03、0.1、0.3和0.6ng/小鼠）。此外，当使用更高剂量的尼古丁时[腹腔注射（0.02、0.03和0.1mg/kg）和脑室内注射（10和24ng/小鼠）]，运动活性降低。然而，单独的尼古丁不会产生动机效应。脑室内注射六甲铵（0.03、0.1和0.3μg/小鼠；在注射尼古丁前10分钟）可减弱尼古丁对吗啡诱导的条件性位置偏爱的影响。腹腔注射六甲铵（1、5和10mg/kg；在注射尼古丁前30分钟）无法获得此效应，脑室内或腹腔注射阿托品（一种毒蕈碱受体拮抗剂）后也无法重现此效应。这些拮抗剂单独使用时未显示出任何动机效应，并且无法影响吗啡诱导的条件性位置偏爱的表达。似乎超低剂量的尼古丁可降低吗啡诱导的位置偏爱表达，并且中枢烟碱型乙酰胆碱受体在这方面发挥作用。
