Several studies have reported that low doses of the 5-HT_1A receptor agonist 8-OH-DPAT reduce cocaine-induced locomotor activity. However, it has also been reported that high doses of 8-OH-DPAT do not substitute for or alter the discriminative signal of cocaine (COC) or amphetamine (AMPH). This study aimed to evaluate the effects of low and high doses of the 5-HT_1A agonist 8-OH-DPAT on the discriminative signal of AMPH using conditioned taste aversion as a drug discrimination procedure. Additionally, to establish a correlation between the behavioral effects in drug discrimination and changes in dopamine (DA) and gamma-aminobutyric acid (GABA) concentrations, we evaluated the effect of systemic administration of low or high doses of the 5-HT_1A receptor agonist 8-OH-DPAT and of the 5-HT_1A receptor antagonist WAY100135 on DA and GABA extracellular concentrations in the nucleus accumbens (nAcc) and ventral tegmental area (VTA), respectively, using cerebral microdialysis. The behavioral results showed that low but not high doses of 8-OH-DPAT produced a reduction in the AMPH-induced discriminative signal, while WAY100135 administration prevented such effects. The microdialysis results showed that a low dose of 8-OH-DPAT decreased extracellular DA concentrations in the nAcc and increased GABA concentrations in the VTA. Pretreatment with WAY100135 prevented these effects. These data support the hypothesis that 5-HT_1A receptors modulate the behavioral effects of psychostimulant drugs, such as AMPH, through somatodendritic 5-HT_1A autoreceptors in the raphe nucleus indicating that 5-HT_1A receptors may be an important target for the development of pharmacological treatments for psychostimulant addiction.

几项研究报告说，低剂量的5-HT _1A受体激动剂8-OH-DPAT降低了可卡因诱导的运动活性。但是，也有报道说高剂量的8-OH-DPAT不能替代或改变可卡因（COC）或苯丙胺（AMPH）的判别信号。这项研究旨在评估低剂量和高剂量的5-HT _1A激动剂8-OH-DPAT对AMPH判别信号的影响，其中使用条件性厌恶作为药物区分程序。此外，为了建立药物歧视的行为效果与多巴胺（DA）和γ-氨基丁酸（GABA）浓度变化之间的相关性，我们评估了低剂量或高剂量5-HT _1A全身给药的效果使用脑微透析分别对伏隔核（nAcc）和腹侧被盖区（VTA）中DA和GABA细胞外浓度的受体激动剂8-OH-DPAT和5-HT _1A受体拮抗剂WAY100135进行了研究。行为结果表明，低剂量但不高剂量的8-OH-DPAT会降低AMPH诱导的歧视性信号，而WAY100135的给药则可防止此类影响。微透析结果表明，低剂量的8-OH-DPAT会降低nAcc中的细胞外DA浓度，并增加VTA中的GABA浓度。用WAY100135进行预处理可防止这些影响。这些数据支持以下假设：5-HT _1A受体通过体树突状5-HT调节精神刺激药物（例如AMPH）的行为效果_图1A中缝核自身受体，表明5-HT _1A受体可以是用于药理治疗的发展对精神兴奋剂成瘾的重要靶标。