Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2013;65(5):1176-84. doi: 10.1016/s1734-1140(13)71475-0.
Methadone is widely accepted as the most effective treatment of opioid dependence. However, clinical observations indicate that the medication is less effective in individuals abusing cocaine. Diminished therapeutic efficacy of methadone in cocaine users is intriguing, but its mechanism has not been studied.
Here, the conditioned place preference (CPP) procedure was used to examine the effects of the dose, number of conditioning sessions and pre-exposure to cocaine on the rewarding effects of morphine and methadone. Vehicle-pre-exposed and cocaine-sensitized mice (five injections of 10 mg/kg over 16 days) were conditioned using methadone (0, 0.1, 0.5, 3, and 5 mg/kg) or morphine (0, 1, and 10 mg/kg). Place preference was measured after one and again after two additional conditioning sessions.
As expected, morphine at 10 mg/kg produced CPP following just one conditioning session. While a single conditioning session with 1 mg/kg of morphine produced no CPP, the rewarding effect became apparent following two additional conditioning sessions as well as in mice pre-exposed to cocaine. Methadone produced CPP following one conditioning session at doses of 0.5, 3 and 5 mg/kg. However, unlike with morphine, methadone's rewarding effect was not enhanced by two additional conditioning sessions or by pre-exposure with cocaine.
Prior exposure to cocaine increases unconditioned motivational effects of morphine but not of methadone.
美沙酮被广泛认为是治疗阿片类药物依赖最有效的方法。然而，临床观察表明，该药在滥用可卡因的个体中效果较差。美沙酮在可卡因使用者中的治疗效果降低令人好奇，但尚未对其机制进行研究。
在这里，使用条件位置偏好（CPP）程序来检查剂量、 Conditioning 次数和可卡因预先暴露对吗啡和美沙酮奖赏作用的影响。用vehicle-pre-exposed 和 cocaine-sensitized 小鼠（在 16 天内注射 5 次 10 mg/kg）用美沙酮（0、0.1、0.5、3 和 5 mg/kg）或吗啡（0、1 和 10 mg/kg）进行 Conditioning。在一次 Conditioning 后测量位置偏好，然后再进行两次。
正如预期的那样，10 mg/kg 的吗啡在仅仅一次 Conditioning 后就产生了 CPP。虽然单次 1 mg/kg 的吗啡 Conditioning 不会产生 CPP，但在两次额外的 Conditioning 后以及在可卡因预先暴露的小鼠中，奖赏效应变得明显。美沙酮在 0.5、3 和 5 mg/kg 的剂量下在一次 Conditioning 后产生 CPP。然而，与吗啡不同，美沙酮的奖赏作用不会因两次额外的 Conditioning 或可卡因预先暴露而增强。
可卡因预先暴露增加了吗啡的非条件动机效应，但不会增加美沙酮的效应。
