Methamphetamine-induced locomotor changes are dependent on age, dose and genotype.
Methamphetamine-induced locomotor changes are dependent on age, dose and genotype.
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DOI：
10.1016/j.pbb.2010.12.004
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Radcliffe RA
中科院分区：
文献类型：
--
作者：
Good RL;Radcliffe RA
青春期是成瘾形成的关键年龄，因为在这段时间内表现出很大比例的病理性药物寻求行为。滥用药物的神经毒性作用在多大程度上影响随后的药物寻求行为和冲动是一个研究不足的领域。甲基苯丙胺（METH）是一种广泛滥用的药物，它会产生从行为敏化到耐受的运动反应，这两种行为都可能与滥用风险有关。在这里，我们调查了年龄，基因型，METH剂量，包括神经毒性剂量，和METH代谢对旷场活动（OFA）的影响，以深入了解药物滥用的复杂疾病。C57 B1/6（B6），DBA/2（D2），和129 S6 SvEv/Tac（129）小鼠品系被给予盐水或高剂量的（4 × 5 mg/kg，间隔2小时，持续2天）或低剂量（2 × 1 mg/kg，间隔24小时）青春期METH预处理（纳塔尔后第40天（PND））或成年早期（PND 80），然后在40天后用METH（1 mg/kg）或盐水攻击进行行为测试。纹状体浓度的甲基和AMPH也进行了测定。重要的调查结果包括：1）METH预处理的青春期B6小鼠由于高剂量METH预处理而对水平运动表现出显著的敏感性; 2）METH预处理的B6成年小鼠对由低剂量METH预处理引起的垂直活动测量表现出显著的耐受性; 3）METH预处理的成年D2小鼠对低剂量METH预处理诱导的垂直活动表现出显著的增敏作用，4）129小鼠代谢METH的速度明显快于B6和D2小鼠，但METH预处理并不改变代谢。在D2青少年研究或129岁年龄组中，未观察到对METH预处理剂量的显著行为反应。我们的研究结果突出了年龄，应变和METH剂量对运动行为结果的相互作用的重要性。
Adolescence is a critical age for addiction formation as a large percentage of pathological drug-seeking behaviors manifest during this time. The extent to which neurotoxic effects of drugs of abuse influence subsequent drug seeking behaviors and impulsivity is an understudied area of research. Methamphetamine (METH) is a widely abused drug that produces locomotor responses ranging from behavioral sensitization to tolerance, both of which are behaviors that may relate to risk of abuse. Here we investigated the effects of age, genotype, METH dose, including a neurotoxic dose, and METH metabolism on open-field activity (OFA) to gain insight into the complex disease of drug abuse. C57Bl/6 (B6), DBA/2 (D2), and 129S6SvEv/Tac (129) mouse strains were administered saline or either a high dose (4 × 5 mg/kg in 2h intervals for 2 days) or low dose (2 × 1 mg/kg in 24h intervals) METH pretreatment during adolescence (post natal day (PND) 40) or early adulthood (PND 80) followed by behavioral testing with a METH (1 mg/kg) or saline challenge 40 days later. Striatal concentrations of METH and AMPH were also determined. Significant findings include: 1) METH pretreated adolescent B6 mice displayed significant sensitization for horizontal locomotion due to high dose METH pretreatment; 2) METH pretreated B6 adults showed significant tolerance for the vertical activity measure caused by low dose METH pretreatment; 3) METH pretreated adult D2 mice exhibited significant sensitization for vertical activity induced by low dose METH pretreatment, and 4) 129 mice metabolized METH significantly faster than the B6 and D2 mice, but METH pretreatment did not alter metabolism. No significant behavioral responses to either METH pretreatment dose were observed for the D2 adolescent studies or either 129 age group. Our results highlight the importance of the interactions of age, strain and METH dose on locomotor behavioral outcomes.
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影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL
影响因子：
17.7
作者：
Kalivas, PW;Volkow, ND
通讯作者：
Volkow, ND
影响因子：
4.8
作者：
Goodwin, J. Shawn;Larson, Gaynor A.;Khoshbouei, Habibeh
通讯作者：
Khoshbouei, Habibeh
影响因子：
3.4
作者：
Hoffman, William F.;Moore, Meredith;Mitchell, Suzanne H.
通讯作者：
Mitchell, Suzanne H.