Asin K E, Montana W E
Department 47U, Abbott Laboratories, Abbott Park, IL 60064.
Pharmacol Biochem Behav. 1989 Apr;32(4):1033-41. doi: 10.1016/0091-3057(89)90077-4.
This series of studies investigated the ability of compounds selective for either the D1 or D2 dopamine receptor to induce a conditioned taste aversion (CTA) in thirsty rats. Neither the D1 antagonist SCH23390 (0.12-0.60 mg/kg) nor the D2 antagonist haloperidol (0.125-0.375 mg/kg) were able to induce CTAs to a saccharin solution. In contrast, the D1 agonist SKF38393 produced a dose-dependent taste aversion which was stereoselective to the (R-) enantiomer. The aversion to (R,S)-SKF38393 was not blocked by pretreatment with either SCH23390 or haloperidol, suggesting that the aversion is not mediated through stimulation of either dopamine receptor subtype. The D2 dopamine receptor agonist quinpirole was also found to produce a dose-dependent CTA. This aversion was blocked by injections of haloperidol and was attenuated following injections of domperidone, suggesting involvement of peripheral dopamine receptors in the aversion. Pretreatment with SCH23390 failed to affect the quinpirole-induced CTA, providing additional evidence that the D1 and D2 dopamine receptor subtypes can function independently of one another in the control of behavior. Finally, it does not appear that the area postrema is importantly involved in these taste aversions since lesions of this brain region did not affect the CTAs induced by either SKF38393 or quinpirole.
这一系列研究调查了对D1或D2多巴胺受体具有选择性的化合物在口渴大鼠中诱导条件性味觉厌恶（CTA）的能力。D1拮抗剂SCH23390（0.12 - 0.60毫克/千克）和D2拮抗剂氟哌啶醇（0.125 - 0.375毫克/千克）均不能诱导对糖精溶液的CTA。相比之下，D1激动剂SKF38393产生了剂量依赖性的味觉厌恶，且对（R-）对映体具有立体选择性。对（R,S）-SKF38393的厌恶不受SCH23390或氟哌啶醇预处理的阻断，这表明该厌恶不是通过刺激任何一种多巴胺受体亚型介导的。还发现D2多巴胺受体激动剂喹吡罗也产生剂量依赖性的CTA。这种厌恶可被氟哌啶醇注射阻断，并在注射多潘立酮后减弱，提示外周多巴胺受体参与了该厌恶过程。用SCH23390预处理未能影响喹吡罗诱导的CTA，这为D1和D2多巴胺受体亚型在行为控制中可相互独立发挥作用提供了额外证据。最后，由于该脑区的损伤并未影响SKF38393或喹吡罗诱导的CTA，所以最后区似乎并未重要参与这些味觉厌恶过程。
