Sahraei Hedayat, Barzegari Amir-Abbas, Shams Jamal, Zarrindast Mohammad-Reza, Haeri-Rohani Ali, Ghoshooni Hassan, Sepehri Houri, Salimi Seyed Hussein
Department of Physiology and Biophysics, Baqiyatallah, University of Medical Sciences, School of Medicine, Baqiyatallah.
Behav Pharmacol. 2006 Nov;17(7):621-8. doi: 10.1097/01.fbp.0000236274.18042.54.
The effect of theophylline on reward properties of morphine was examined in the present study. A biased conditioned place preference paradigm was used to study the effects of theophylline on the development of conditioned place preference by morphine in sensitized and tolerant female mice. Subcutaneous injection of morphine (0.5-10 mg/kg) induced conditioned place preference in mice, while intraperitoneal administration of theophylline (2.5-100 mg/kg) did not induce conditioned place preference or conditioned place aversion. Theophylline (2.5-100 mg/kg) in combination with morphine (5 mg/kg), during conditioning sessions, decreased the acquisition of morphine conditioned place preference dose independently. Administration of theophylline (2.5-100 mg/kg) before testing also caused a significant reduction of the expression of morphine-induced conditioned place preference in a dose-independent manner. Administration of morphine (12.5, 25 or 50 mg/kg) daily, for 3 days, produced tolerance to conditioned place preference induced by the drug (5 mg/kg). Administration of theophylline (2.5 and 10 mg/kg) 1 h before morphine (12.5, 25 mg/kg), during development of tolerance, abolished morphine tolerance. A higher dose of theophylline (100 mg/kg), however, did not alter morphine tolerance. In addition, theophylline (2.5, 10 and 100 mg/kg) failed to reduce tolerance to a higher dose of morphine (50 mg/kg). Daily administration of morphine (5 mg/kg) for 3 days followed by a 5-day interval caused sensitization to morphine place conditioning. When theophylline was administered (2.5, 10 and 100 mg/kg) 1 h before morphine (5 mg/kg), during development of sensitization, inhibition of morphine-induced sensitization was demonstrated. The effect of theophylline was dose independent. It is concluded that while theophylline has no effect by itself, it reduced both the acquisition and expression of morphine conditioned place preference. In addition, theophylline reduced the acquisition of morphine conditioned place preference in morphine-sensitized and morphine-tolerant mice.
本研究考察了茶碱对吗啡奖赏特性的影响。采用偏倚条件性位置偏爱范式，研究茶碱对致敏和耐受雌性小鼠中吗啡诱导的条件性位置偏爱的影响。皮下注射吗啡（0.5 - 10毫克/千克）可诱导小鼠产生条件性位置偏爱，而腹腔注射茶碱（2.5 - 100毫克/千克）既不诱导条件性位置偏爱也不诱导条件性位置厌恶。在条件训练期间，茶碱（2.5 - 100毫克/千克）与吗啡（5毫克/千克）联合使用，可剂量依赖性地降低吗啡条件性位置偏爱的获得。在测试前给予茶碱（2.5 - 100毫克/千克）也以剂量非依赖性方式显著降低了吗啡诱导的条件性位置偏爱的表达。每天注射吗啡（12.5、25或50毫克/千克），持续3天，可产生对该药物（5毫克/千克）诱导的条件性位置偏爱的耐受。在耐受形成过程中，在吗啡（12.5、25毫克/千克）前1小时给予茶碱（2.5和10毫克/千克），可消除吗啡耐受。然而，更高剂量的茶碱（100毫克/千克）并未改变吗啡耐受。此外，茶碱（2.5、10和100毫克/千克）未能降低对更高剂量吗啡（50毫克/千克）的耐受。每天注射吗啡（5毫克/千克），持续3天，随后间隔5天，可导致对吗啡位置条件化的致敏。在致敏形成过程中，当在吗啡（5毫克/千克）前1小时给予茶碱（2.5、10和100毫克/千克）时，可证明对吗啡诱导的致敏有抑制作用。茶碱的作用是非剂量依赖性的。结论是，虽然茶碱本身没有作用，但它降低了吗啡条件性位置偏爱的获得和表达。此外，茶碱降低了吗啡致敏和吗啡耐受小鼠中吗啡条件性位置偏爱的获得。
