Rezayof Ameneh, Nazari-Serenjeh Farzaneh, Zarrindast Mohammad-Reza, Sepehri Houri, Delphi Ladan
School of Biology, University College of Science, University of Tehran, Tehran, Iran.
Eur J Pharmacol. 2007 May 7;562(1-2):92-102. doi: 10.1016/j.ejphar.2007.01.081. Epub 2007 Feb 8.
In the present study, the effects of intra-ventral tegmental area injections of cholinergic agents on morphine-induced conditioned place preference were investigated by using an unbiased 3-day schedule of place conditioning design in rats. The conditioning treatments with subcutaneous injections of morphine (0.5-7.5 mg/kg) induced a significant dose-dependent conditioned place preference for the drug-associated place. Intra-ventral tegmental area injection of an anticholinesterase, physostigmine (2.5 and 5 microg/rat) or nicotinic acetylcholine receptor agonist, nicotine (0.5 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant conditioned place preference. Furthermore, intra-ventral tegmental area administration of muscarinic acetylcholine receptor antagonist, atropine (1-4 microg/rat) or nicotinic acetylcholine receptor antagonist, mecamylamine (5 and 7.5 microg/rat) dose-dependently inhibited the morphine (5 mg/kg)-induced place preference. Atropine or mecamylamine reversed the effect of physostigmine or nicotine on morphine response respectively. The injection of physostigmine, but not atropine, nicotine or mecamylamine, into the ventral tegmental area alone produced a significant place aversion. Moreover, intra-ventral tegmental area administration of the higher doses of physostigmine or atropine, but not nicotine or mecamylamine decreased the locomotor activity. We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine.
在本研究中，通过使用无偏倚的为期3天的位置条件化设计，研究了向大鼠腹侧被盖区注射胆碱能药物对吗啡诱导的条件性位置偏爱效应的影响。皮下注射吗啡（0.5 - 7.5毫克/千克）进行条件化处理，可诱导出对药物相关位置的显著剂量依赖性条件性位置偏爱。向腹侧被盖区注射抗胆碱酯酶药物毒扁豆碱（2.5和5微克/只大鼠）或烟碱型乙酰胆碱受体激动剂尼古丁（0.5和1微克/只大鼠）与无效剂量的吗啡（0.5毫克/千克）一起，可引发显著的条件性位置偏爱。此外，向腹侧被盖区给予毒蕈碱型乙酰胆碱受体拮抗剂阿托品（1 - 4微克/只大鼠）或烟碱型乙酰胆碱受体拮抗剂美加明（5和7.5微克/只大鼠），可剂量依赖性地抑制吗啡（5毫克/千克）诱导的位置偏爱。阿托品或美加明分别逆转了毒扁豆碱或尼古丁对吗啡反应的影响。单独向腹侧被盖区注射毒扁豆碱，而不是阿托品、尼古丁或美加明，会产生显著的位置厌恶。此外，向腹侧被盖区给予较高剂量的毒扁豆碱或阿托品，但不是尼古丁或美加明，会降低运动活性。我们得出结论，腹侧被盖区的毒蕈碱型和烟碱型乙酰胆碱受体可能在关键程度上介导了吗啡的奖赏效应。
