Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats
Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats
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DOI：
10.4062/biomolther.2014.056
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发表时间：
2014-09-30
影响因子：
3.7
通讯作者：
Cheong, Jae Hoon
中科院分区：
文献类型：
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作者：
Ahsan, Hafiz Muhammad;de la Pena, June Bryan I.;Cheong, Jae Hoon
尼古丁成瘾是一个世界性的问题。然而，先前在动物模型中描述尼古丁的奖励和强化作用的研究报告了不一致的结果。据观察，成瘾作用因不同因素（如给药途径、剂量和年龄）而异。在这里，我们评估了尼古丁在不同给药途径、广泛剂量范围和不同年龄组中的奖励和强化作用。两个最广泛使用的药物成瘾的动物模型：条件性位置偏爱（CPP）和自我管理（SA）测试。在不同途径[腹膜内（i.p.）和皮下（s.c.）]，剂量（0.05 - 1.0 mg/kg）和年龄[青春期和成年大鼠]。同样，在不同剂量（0.01 - 0.06 mg/kg/输注）和年龄（青少年和成年大鼠）下评估了静脉内尼古丁SA。在CPP测试中，s.c.尼古丁产生的反应比腹腔注射更大。0.2 mg/kg剂量在青少年中产生最高的CPP反应，而在成年大鼠中产生最高的CPP反应;这也在7天预处理大鼠中得到证实。在SA试验中，青春期大鼠容易自我给予0.03 mg/kg/输注尼古丁。产生尼古丁CPP和SA的剂量诱导的血液尼古丁水平与人类吸烟者相当。总之，我们已证明尼古丁可产生可靠的CPP [0.2 mg/kg剂量（s.c.）]青少年和[0.6 mg/kg剂量（皮下）]成年大鼠和青春期大鼠中的SA [0.03 mg/kg/输注]。这两项测试都表明，青春期的老鼠对尼古丁的奖励和强化作用更敏感。
Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine.