The role of the frontal cortex in the mouse in behavioral sensitization to amphetamine
The role of the frontal cortex in the mouse in behavioral sensitization to amphetamine
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DOI：
10.1016/s0006-8993(97)00221-7
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发表时间：
1997-05-23
期刊：
影响因子：
2.9
通讯作者：
Calder, LD
中科院分区：
文献类型：
--
作者：
Karler, R;Bedingfield, JB;Calder, LD
药理学研究表明，多种神经效应器参与了对苯丙胺诱导的刻板印象的行为敏化。在本工作中，研究了其中一些药物在皮质内给药后对致敏的影响，以确定皮质在调节其全身效应中的作用。多巴胺拮抗剂舒必利和螺环酮对苯丙胺的急性反应均无效，但两者均阻断了敏化的诱导，提示大脑皮层多巴胺通路不参与急性反应，但对敏化的诱导是必要的。NMDA受体拮抗剂CPP和GABA(A)激动剂THIP均阻断了苯丙胺的急性反应和敏化诱导。另一方面，烟碱胆碱能拮抗剂甲乙胺既不影响急性反应，也不影响致敏诱导，这表明大脑皮层不是其活动的场所。蛋白质合成的抑制剂茴香霉素和钙通道阻滞剂地尔硫卓都对急性反应无效，但都阻断了诱导。除CPP和THIP外，所有药物均对致敏基因的表达无效，因此，其他药物阻断表达的能力必须位于另一个基因座上。皮下注射非惊厥剂量的荷包牡丹碱产生的刻板印象与安非他明诱导的刻板印象难以区分：这种作用很容易被全身或皮质内注射的CPP所拮抗。相反，舒必利无论通过哪种给药途径都不能阻断荷包牡丹碱诱导的刻板印象；因此，我们得出结论，荷包牡丹碱的刻板印象效应不是由多巴胺介导的。这些结果表明，苯丙胺诱导的刻板印象是通过去除兴奋系统的抑制控制而在大脑皮层中介导的。数据还表明，皮质多巴胺以及NMDA和GABA(A)系统在苯丙胺的敏化过程中起着重要作用。总体而言，这些数据表明，参与敏化的不同神经效应器在不同的大脑部位发挥作用。
Pharmacological studies have shown that a variety of neuroeffectors are involved in behavioral sensitization to amphetamine-induced stereotypy. In the present work, the effect of some of these drugs on sensitization was studied after intracortical administration in order to determine the role of the cortex in mediating their systemic effects. The dopamine antagonists sulpiride and spiperone were both ineffective against the acute response to amphetamine: nevertheless, both blocked the induction of sensitization, suggesting that the mesocortical dopamine pathway is not involved in the acute response but is necessary for the induction of sensitization. Both CPP, an NMDA receptor antagonist, and THIP, a GABA(A) agonist, blocked the acute response and the induction of sensitization to amphetamine. On the other hand, mecamylamine, the nicotinic cholinergic antagonist, failed to affect either the acute response or the induction of sensitization, which suggests that the cortex is not a locus of its activity. Anisomycin, an inhibitor of protein synthesis, and diltiazem, a calcium-channel blocker, were both ineffective against the acute response, but both blocked induction. All of the drugs, except CPP and THIP, were ineffective against the expression of sensitization; therefore, the ability of the other drugs to block expression must reside within another locus. Bicuculline injected intracortically in non-convulsant doses produced a stereotypy indistinguishable from that induced by amphetamine: and the effect was readily antagonized by CPP administered either systemically or intracortically. In contrast, sulpiride by either route of administration failed to block the bicuculline-induced stereotypy; we conclude, therefore, that the stereotypic effect of bicuculline is not mediated by dopamine. These results imply that amphetamine-induced stereotypy is mediated in the cortex by the removal of the inhibitory control of the excitatory system. The data also suggest that cortical dopamine, as well as the NMDA and GABA(A) systems, is important in sensitization to amphetamine. In general the data demonstrate that different neuroeffectors involved in sensitization exert their effects at different brain loci.