Tran Steven, Facciol Amanda, Gerlai Robert
Department of Cell and Systems Biology, University of Toronto Mississauga, 3359 Mississauga Road North, DV 1022D, Mississauga, Ontario, L5L 1C6, Canada.
Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada.
Psychopharmacology (Berl). 2016 Jun;233(11):2119-2128. doi: 10.1007/s00213-016-4264-3. Epub 2016 Mar 9.
The dopaminergic system has been proposed to mediate alcohol-induced locomotor activity, yet the mechanisms underlying this behavioral response remain poorly understood.
This study was conducted to investigate the role of dopamine D2-like receptors in mediating alcohol-induced behavioral responses.
In experiment 1, we examined the effects of high concentrations (0, 2.5, 5, 10 μM) of haloperidol on motor responses. In experiment 2, we examined the effects of low concentrations (0, 0.625, 1.25, 2.5 μM) of haloperidol on anxiety-like behavioral responses using the novel tank test. In experiment 3, we examined the effect of pre-treating zebrafish with different concentrations of haloperidol (0, 0.625, 2.5 μM) and subsequently exposing them to 0 or 1 % alcohol.
In experiment 1, haloperidol induced an inverted U-shaped concentration-dependent increase in locomotor activity. In experiment 2, haloperidol (2.5 μM) reduced the absolute turn angle and freezing behavior in a new environment. In experiment 3, acute alcohol exposure significantly increased locomotor activity and decreased anxiety-like behavioral responses. Pre-treating zebrafish with the lower dose of haloperidol (0.625 μM) abolished the alcohol-induced locomotor activity, without altering anxiety-like behavioral responses. However, pre-treating with the higher dose of haloperidol (2.5 μM) abolished both alcohol-induced increase of locomotor activity and reduction of anxiety-like behavioral responses.
The results suggest alcohol-induced locomotor hyperactivity in zebrafish is mediated via activation of dopamine D2-like receptors, whereas anxiety-like behavioral responses may only be altered by a high haloperidol concentration, at which dose the drug may affect receptors other than D2-R.
多巴胺能系统被认为介导酒精诱导的运动活动，但这种行为反应背后的机制仍知之甚少。
本研究旨在探讨多巴胺D2样受体在介导酒精诱导的行为反应中的作用。
在实验1中，我们研究了高浓度（0、2.5、5、10 μM）氟哌啶醇对运动反应的影响。在实验2中，我们使用新水箱试验研究了低浓度（0、0.625、1.25、2.5 μM）氟哌啶醇对焦虑样行为反应的影响。在实验3中，我们研究了用不同浓度氟哌啶醇（0、0.625、2.5 μM）预处理斑马鱼，随后将它们暴露于0%或1%酒精中的效果。
在实验1中，氟哌啶醇诱导运动活动呈倒U形浓度依赖性增加。在实验2中，氟哌啶醇（2.5 μM）减少了新环境中的绝对转弯角度和僵住行为。在实验3中，急性酒精暴露显著增加了运动活动并减少了焦虑样行为反应。用较低剂量氟哌啶醇（0.625 μM）预处理斑马鱼可消除酒精诱导的运动活动，而不改变焦虑样行为反应。然而，用较高剂量氟哌啶醇（2.5 μM）预处理可消除酒精诱导的运动活动增加和焦虑样行为反应减少。
结果表明，斑马鱼中酒精诱导的运动亢进是通过多巴胺D2样受体的激活介导的，而焦虑样行为反应可能仅在高氟哌啶醇浓度下改变，在该剂量下药物可能影响除D2-R以外的受体。
