FES Iztacala, Universidad Nacional Autónoma de México, Av. de los Barrios 1, Los Reyes Iztacala, 54090, Tlalnepantla de Baz, Edo de México, Mexico.
Exp Brain Res. 2019 Jul;237(7):1691-1697. doi: 10.1007/s00221-019-05540-z. Epub 2019 Apr 15.
GABA and 5-HT agonists are effective in attenuating the behavioral effects of psychostimulants. However, they induce adverse side effects when used in high doses. The previous evidence has suggested that the 5HT receptor activation effect could be produced by an increased release of GABA in the ventral tegmental area (VTA) and the consequent activation of GABAergic receptors. Therefore, the objective of this study was to evaluate the effects of joint administration of an intermediate dose of the GABA agonist baclofen (3.0 mg/kg) with different doses of the 5HT agonist Ro60-0175 (0.3, 1.0, and 3.0 mg/kg) on the locomotor sensitization expression induced by the repeated administration of amphetamine (1.0 mg/kg). Our results showed an attenuation of the expression of sensitization in a dose-dependent manner with both agonists. In both cases, we observed a complete blockade at the highest dose. In addition, the intermediate dose of baclofen increased the effects of the three doses of Ro60-0175. These results support the role of the joint action of GABA and 5-HT receptors in the effects of psychostimulants. However, it remains to be explored whether the observed effect can be attributed to receptors located in the VTA or the nucleus accumbens.
GABA 和 5-HT 激动剂可有效减轻精神兴奋剂的行为效应。然而，当高剂量使用时，它们会引起不良反应。先前的证据表明，5-HT 受体的激活作用可能是由于腹侧被盖区（VTA）中 GABA 释放增加，继而激活 GABA 能受体所致。因此，本研究的目的是评估中等剂量 GABA 激动剂巴氯芬（3.0mg/kg）与不同剂量 5-HT 激动剂 Ro60-0175（0.3、1.0 和 3.0mg/kg）联合给药对反复给予安非他命（1.0mg/kg）诱导的运动敏化表达的影响。我们的结果表明，两种激动剂均以剂量依赖性方式减弱敏化表达。在这两种情况下，我们在最高剂量下观察到完全阻断。此外，中等剂量的巴氯芬增加了 Ro60-0175 的三种剂量的作用。这些结果支持 GABA 和 5-HT 受体的联合作用在精神兴奋剂效应中的作用。然而，仍需要探讨观察到的效应是否归因于位于 VTA 或伏隔核的受体。
