Neonatal isolation alters the estrous cycle interactions on the acute behavioral effects of cocaine
Neonatal isolation alters the estrous cycle interactions on the acute behavioral effects of cocaine
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DOI：
10.1016/j.psyneuen.2005.03.004
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发表时间：
2005-09-01
影响因子：
3.7
通讯作者：
Kehoe, P
中科院分区：
文献类型：
--
作者：
Kosten, TA;Sanchez, H;Kehoe, P
我们证明，新生儿隔离（ISO）增加收购可卡因自我管理和改变精神兴奋剂诱导的腹侧纹状体多巴胺和5-羟色胺水平的雌性大鼠。多巴胺和5-羟色胺都调节可卡因的行为效应，这些效应在发情阶段会有所不同。我们现在测试是否ISO修改的方式，动情阶段影响可卡因的急性行为反应。将窝仔分配至ISO（1小时/天隔离;出生后第2-9天）或非处理（NH）条件。在实验1中，评估了可卡因（0.3-30 mg/kg; IP）在动情前期、动情期和间情期破坏食物时间表控制反应的能力。与基线相比，发情间期和发情前期NH雌性动物在低剂量可卡因下的反应率增加，在高剂量下的反应率降低。相比之下，发情期NH雌性动物在所有剂量下均显示反应降低。ISO消除了这种发情阶段的区别，只有减少响应高可卡因剂量。然而，在食物限制（实验2）的发情周期没有不同的组。为了证实这种ISO效应，在实验3中对发情前期或发情期大鼠给予可卡因（0、5、10 mg/kg; IP）并监测活动。自发活动不同的发情期NH，但ISO大鼠。在峰值行为活动时的血浆皮质醇水平（实验4）没有组或发情阶段的差异。结果扩展了先前的研究，表明发情期会改变可卡因的行为效应。新生儿隔离消除了这些影响，可能反映了多巴胺单胺水平的改变或雌激素对该系统的影响。(c)2005爱思唯尔有限公司保留所有权利。
We demonstrated that neonatal isolation (ISO) increases acquisition of cocaine self-administration and alters psychostimulant-induced ventral striatal dopamine and serotonin levels in female rats. Both dopamine and serotonin modulate the behavioral effects of cocaine and these effects can vary across estrous stages. We now test whether ISO modifies the manner in which estrous stage affects the acute behavioral responses to cocaine. Litters were assigned to ISO (1 h/day isolation; post-natal days 2-9) or non-handled (NH) conditions. In Experiment 1, the ability of cocaine (0.3-30 mg/kg; IP) to disrupt schedule-controlled responding for food was assessed in proestrus, estrus, and diestrus stages. Diestrus and proestrus NH females showed increased response rates at low cocaine doses and decreased rates at higher doses relative to baseline. In contrast, estrus NH females showed decreased responding across all doses. ISO eliminated this estrous stage distinction; only decreased responding to high cocaine doses were seen. Yet, estrous cyclicity during food restriction (Experiment 2) did not differ by group. To confirm this ISO effect, proestrus or estrus rats were administered cocaine (0, 5, 10 mg/kg; IP) and activity monitored in Experiment 3. Locomotor activity differed by estrous stage in NH but not ISO rats. Cocaine plasma levels (Experiment 4) at the time of peak behavioral activity did not differ by group or estrous stage. Results extend prior studies to show estrous stage alters the behavioral effects of cocaine. Neonatal isolation eliminates these effects perhaps reflecting alterations in accumbens monoamine levels or the effects of estrogen on this system. (c) 2005 Elsevier Ltd. All rights reserved.