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首页> 外文期刊>Addiction biology >Endogenous GDNF in ventral tegmental area and nucleus accumbens does not play a role in the incubation of heroin craving.
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Endogenous GDNF in ventral tegmental area and nucleus accumbens does not play a role in the incubation of heroin craving.

机译：腹侧被盖区和伏隔核中的内源性GDNF在海洛因渴望的孵化中不起作用。

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摘要

Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 microg/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving.
机译：腹侧被盖区（VTA）中胶质细胞源性神经营养因子（GDNF）的活性介导了戒断诱导的可卡因寻找后的时间依赖性增加（对可卡因的渴望培养）。在这里，我们研究了这些发现对培养海洛因渴望的普遍性。训练大鼠自用海洛因10天（6小时/天; 0.075 mg / kg /输注;输注与声调提示配对），并在1，11之后的灭绝测试中测试提示的海洛因诱导寻找或30个提款日。提示诱导的海洛因寻求在11或30天后要比1天（孵化海洛因后）要高，并且消光响应的时间依赖性增加与VTA和伏隔核中GDNF mRNA表达的时间依赖性变化有关。此外，在最后一次海洛因自我管理培训课程后的1-3小时内给予AccuAccumbens（但不是VTA）GDNF注射（12.5微克/侧）可增加停药后对灭绝反应的时间依赖性增加。然而，停药后消光反应的时间依赖性增加与VTA和伏隔动物中GDNF蛋白表达的变化无关。此外，通过将抗GDNF单克隆中和抗体（600 ng /边/天）长期递送到VTA或伏安中来干扰内源性GDNF功能，对灭绝反应的时间依赖性增加没有影响。总之，海洛因的自我管理和戒断以时间依赖性的方式调节VTA和伏隔GDNF mRNA的表达，外源性GDNF向伏隔而不是VTA的施用增强了线索诱导的海洛因搜寻。但是，基于GDNF蛋白的表达和抗GDNF单克隆中和抗体的操作数据，我们得出结论，伏伏菌和VTA内源性GDNF都不介导海洛因渴望的培养。

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