Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking.
Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking.
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DOI：
10.1016/j.pbb.2013.09.009
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发表时间：
2013-11
影响因子：
3.6
通讯作者：
Neumaier, John F.
中科院分区：
文献类型：
--
作者：
Nair, Sunila G.;Furay, Amy R.;Liu, Yusha;Neumaier, John F.
关键词：
5-HT 1B受体在从丘脑核壳（NAccSh）投射到腹侧被盖区的中型多刺神经元的终末上密集表达，其中5-HT 1B受体直接调节GABA释放，并间接调节多巴胺能神经元的放电。虽然NAccSh 5-HT 1B受体和压力之间的相互作用已被报道在精神兴奋剂诱导的神经适应的早期阶段，特别是精神敏化，这种相互作用对药物寻求的后期阶段的影响目前尚不清楚。在这里，我们研究了单纯疱疹病毒（HSV）介导的NAccSh 5-HT 1B受体过表达对恢复可卡因寻求暴露于压力或可卡因总理诱导的影响。训练大鼠自我给予可卡因（0.75 mg/kg/输注），并消除操作性反应。然后将表达5-HT 1B和绿色荧光蛋白（GFP）的病毒载体或单独的GFP注射到大鼠的NAccSh中。评估了5-HT 1B受体过表达对间歇性足电击（0.5 mA持续15分钟）或可卡因引发（10 mg/kg，ip）诱导的恢复的影响。结果表明，NAccSh 5-HT 1B受体过表达对足电击恢复没有影响，而显著降低可卡因引发诱导的恢复。我们还发现，5-HT 1B受体的NAccSh过表达对社交失败压力后的糖精摄入量没有影响。这些结果表明，靶向5-HT 1B受体的药物治疗可卡因复吸的功效将在很大程度上取决于恢复刺激的性质。与以前的结果一起，似乎NAccSh 5-HT 1B受体影响应激反应的早期，但不是在后期阶段的精神兴奋剂诱导的神经适应。
5-HT1B receptors are densely expressed on terminals of medium spiny neurons projecting from the nucleus accumbens shell (NAccSh) to the ventral tegmental area, where 5-HT1B receptors modulate GABA release directly, and firing of dopaminergic neurons indirectly. While interactions between NAccSh 5-HT1B receptors and stress have been reported in early stages of psychostimulant-induced neuroadaptations, specifically psychomotor sensitization, the effect of this interaction on later stages of drug seeking is currently unknown. Here, we examined the effect of herpes simplex virus (HSV)-mediated overexpression of NAccSh 5-HT1B receptors on reinstatement of cocaine seeking induced by exposure to stress or a cocaine prime. Rats were trained to self-administer cocaine (0.75 mg/kg/infusion) and the operant response was extinguished. Rats were then injected with viral vector expressing 5-HT1B and green fluorescent protein (GFP) or GFP alone into the NAccSh. The effect of 5-HT1B receptor overexpression was assessed on reinstatement induced by intermittent footshock (0.5 mA for 15 minutes) or a cocaine prime (10 mg/kg, ip). Results indicate that NAccSh 5-HT1B receptor overexpression had no effect on footshock reinstatement while significantly decreasing cocaine priming-induced reinstatement. We also found that NAccSh overexpression of 5-HT1B receptors had no effect on saccharin intake following social defeat stress. These results suggest that the efficacy of pharmacological agents targeting 5-HT1B receptors for the treatment of cocaine relapse will depend largely on the nature of the reinstating stimulus. Taken together with previous results it appears that NAccSh 5-HT1B receptors influence stress responses in early, but not in the later stages of psychostimulant-induced neuroadaptations.
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DOI：
10.3109/10826089409047904
发表时间：
1994-01-01
期刊：
INTERNATIONAL JOURNAL OF THE ADDICTIONS
影响因子：
--
作者：
DEJONG, W
通讯作者：
DEJONG, W
影响因子：
3.4
作者：
Erb, S;Shaham, Y;Stewart, J
通讯作者：
Stewart, J
影响因子：
5.3
作者：
Clark, MS;Sexton, TJ;Neumaier, JF
通讯作者：
Neumaier, JF
影响因子：
17.7
作者：
Kalivas, PW;Volkow, ND
通讯作者：
Volkow, ND
影响因子：
3.6
作者：
Morikawa, H;Manzoni, OJ;Williams, JT
通讯作者：
Williams, JT