Department of Pharmacology, University of Helsinki, Helsinki, Finland.
J Psychopharmacol. 2019 Jul;33(7):855-864. doi: 10.1177/0269881119844178. Epub 2019 May 9.
Alcohol use associates with environmental cues that can later reinstate drinking patterns without any alcohol exposure. Alcohol-induced reward, when combined with contextual signals of various sensory modalities in the central synapses of mesolimbic reward circuitries, can lead to the formation of conditioned responses.
As the activation of glutamatergic synapses is pivotal in such processes, we aimed to investigate whether the metabotropic glutamate receptor subtype 3 plays a role in alcohol-induced behaviours including place preference.
The metabotropic glutamate receptor subtype 3 knockout (mGluR3-KO) mouse line was used to study alcohol-induced place preference, locomotor activating and ataxic effects, limited access alcohol drinking, and preference for sucrose and saccharin.
Alcohol-induced horizontal locomotor stimulation and reduced rearing behaviour remained unchanged in the mGluR3-KO mice. However, alcohol-induced place conditioning in an unbiased paradigm setup was lacking in the mGluR3-KO mice, but clearly present in wildtype mice. Locomotor activity was not different between the mGluR3-KO and wildtype mice during the acquisition and expression trials. Alcohol consumption, studied through the 'drinking in the dark' model, remained unchanged in the mGluR3-KO mice, although low consumption in both wildtype and knockout mice hampers interpretation. The mGluR3-KO mice also showed normal sucrose and saccharin preference.
These studies indicate a role for metabotropic glutamate receptor subtype 3 in the conditioned contextual alcohol responses, but not in stimulatory, and ataxic alcohol effects.
酒精的使用与环境线索有关，这些线索在没有任何酒精暴露的情况下可以重新恢复饮酒模式。当酒精引起的奖赏与中脑边缘奖赏回路中枢突触中各种感觉模态的上下文信号结合时，可能会导致条件反应的形成。
由于谷氨酸能突触的激活在这些过程中至关重要，我们旨在研究代谢型谷氨酸受体亚型 3 是否在包括位置偏好在内的酒精诱导行为中发挥作用。
使用代谢型谷氨酸受体亚型 3 敲除（mGluR3-KO）小鼠品系研究酒精诱导的位置偏好、运动激活和共济失调效应、有限接触酒精饮用以及对蔗糖和糖精的偏好。
mGluR3-KO 小鼠中酒精诱导的水平运动刺激和减少的后肢抬高行为没有改变。然而，在无偏置范式设置中，mGluR3-KO 小鼠中缺乏酒精诱导的位置条件反射，但在野生型小鼠中明显存在。在获得和表达试验中，mGluR3-KO 小鼠和野生型小鼠的运动活性没有差异。通过“暗饮”模型研究的酒精消耗在 mGluR3-KO 小鼠中没有改变，尽管野生型和敲除小鼠的低消耗阻碍了解释。mGluR3-KO 小鼠也表现出正常的蔗糖和糖精偏好。
这些研究表明代谢型谷氨酸受体亚型 3 在条件性上下文酒精反应中起作用，但在刺激和共济失调的酒精效应中不起作用。
