Increased expression of 5-HT6 receptors in the nucleus accumbens blocks the rewarding but not psychomotor activating properties of cocaine
Increased expression of 5-HT6 receptors in the nucleus accumbens blocks the rewarding but not psychomotor activating properties of cocaine
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DOI：
10.1016/j.biopsych.2007.02.018
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发表时间：
2008-01-15
影响因子：
10.6
通讯作者：
Neumaier, John F.
中科院分区：
文献类型：
--
作者：
Ferguson, Susan M.;Mitchell, Ellen S.;Neumaier, John F.
背景资料：重复接触可卡因会产生持久形式的药物经验依赖性行为可塑性，包括条件性位置偏好（CPP）和精神敏感性，可卡因的精神激活效应逐渐持续增加。尽管5-羟色胺-6受体（5-HT（6）Rs）在被认为是这些现象的基础的脑区域（如延髓核（NAc））中大量表达，但令人惊讶的是，关于5-HT（6）Rs在可卡因的奖赏和精神激活效应中的作用知之甚少。结果：5-HT（6）Rs在NAc中的表达增加可阻断对可卡因的CPP，但对可卡因的急性运动反应和可卡因诱导的运动敏感性的发展均无影响。此外，5-HT（6）Rs的拮抗作用促进了对可卡因的CPP的获得，但对可卡因诱导的stereotypy.Conclusions没有影响：这些结果表明，5-HT（6）Rs在NAc可以选择性地调节药物奖励，可能通过促进奖励学习。
Background: Repeated exposure to cocaine produces enduring forms of drug experience-dependent behavioral plasticity, including conditioned place preference (CPP) and psychomotor sensitization, a progressive and persistent increase in cocaine's psychomotor activating effects. Although serotonin-6 receptors (5-HT(6)Rs) are abundantly expressed in the brain regions thought to underlie these phenomena, such as the nucleus accumbens (NAc), surprisingly little is known about the role of 5-HT(6)Rs in the rewarding and psychomotor activating effects of cocaine.Methods: Viral-mediated gene transfer was used to selectively increase 5-HT6R expression in the NAc of rats. The effects of 5-HT6R overexpression and the selective 5-HT6R antagonist Ro4368554 on CPP and psychomotor sensitization were examined.Results: Increased expression of 5-HT(6)Rs in the NAc blocks a CPP to cocaine but has no effect on either the acute locomotor response to cocaine or on the development of cocaine-induced locomotor sensitization. Furthermore, antagonism of 5-HT(6)Rs facilitates the acquisition of a CPP to cocaine but has no effect on cocaine-induced stereotypy.Conclusions: These results demonstrate that 5-HT(6)Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.