Ethanol and Caffeine Effects on Social Interaction and Recognition in Mice: Involvement of Adenosine A(2A) and A(1) Receptors.

Ethanol and Caffeine Effects on Social Interaction and Recognition in Mice: Involvement of Adenosine A(2A) and A(1) Receptors.
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DOI:
10.3389/fnbeh.2016.00206
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发表时间:
2016
影响因子:
3
通讯作者:
Correa M
Correa M
中科院分区:
医学3区
文献类型:
--
作者:
López-Cruz L;San-Miguel N;Bayarri P;Baqi Y;Müller CE;Salamone JD;Correa M

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乙醇和咖啡因经常结合使用,对腺苷系统有相反的影响:乙醇代谢导致腺苷水平增加,而咖啡因是一种非选择性腺苷A1/A2 A受体拮抗剂。这些受体在纹状体和嗅结节中高度表达,这些脑区涉及啮齿动物的探索和社会互动。乙醇调节社会互动过程,但腺苷在社会行为中的作用仍然知之甚少。本研究旨在研究乙醇、咖啡因及其组合对社会行为的影响,并探讨A1和A2 A受体在这些行为中的作用。雄性CD 1小鼠进行了评估,在社会互动三室范例,偏好的同种与对象,也为长期识别记忆的熟悉与新的同种。乙醇表现出双相效应,低剂量(0.25 g/kg)增加社会接触,高剂量(1.0-1.5 g/kg)减少社会互动。然而,没有剂量改变社会偏好;小鼠总是花更多的时间嗅同种比对象,独立的乙醇剂量。乙醇,即使在不改变社会探索的剂量下,也会在第二天对社会认知产生遗忘效应。咖啡因减少了社会接触(15.0-60.0 mg/kg),甚至在更高剂量(30.0-60.0 mg/kg)时阻止了社会偏好。A1拮抗剂环戊基茶碱(CPT; 3-9 mg/kg)本身不改变社会接触或偏好,A2 A拮抗剂MSX-3(1.5-6 mg/kg)在所有剂量下均增加社会互动。中等剂量的乙醇(0.5-1.0 g/kg)能够逆转咖啡因(15.0-30.0 mg/kg)引起的社会探索减少。虽然在第一天的社会探索中,乙醇和CPT或MSX-3之间没有相互作用,但MSX-3阻断了第二天观察到的乙醇的遗忘作用。因此,乙醇损害社会记忆的形成,A2 A腺苷拮抗剂可以防止乙醇的遗忘作用,使动物能够识别熟悉的同种。另一方面,乙醇可以对抗咖啡因(一种非选择性腺苷A1/A2 A受体拮抗剂)引起的社交退缩。这些结果显示了乙醇和咖啡因之间复杂的相互作用,其中一些可能是它们在调节腺苷系统中的相反作用的结果。
Ethanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olfactory tubercle, brain areas involved in exploration and social interaction in rodents. Ethanol modulates social interaction processes, but the role of adenosine in social behavior is still poorly understood. The present work was undertaken to study the impact of ethanol, caffeine and their combination on social behavior, and to explore the involvement of A1 and A2A receptors on those actions. Male CD1 mice were evaluated in a social interaction three-chamber paradigm, for preference of conspecific vs. object, and also for long-term recognition memory of familiar vs. novel conspecific. Ethanol showed a biphasic effect, with low doses (0.25 g/kg) increasing social contact and higher doses (1.0–1.5 g/kg) reducing social interaction. However, no dose changed social preference; mice always spent more time sniffing the conspecific than the object, independently of the ethanol dose. Ethanol, even at doses that did not change social exploration, produced amnestic effects on social recognition the following day. Caffeine reduced social contact (15.0–60.0 mg/kg), and even blocked social preference at higher doses (30.0–60.0 mg/kg). The A1 antagonist Cyclopentyltheophylline (CPT; 3–9 mg/kg) did not modify social contact or preference on its own, and the A2A antagonist MSX-3 (1.5–6 mg/kg) increased social interaction at all doses. Ethanol at intermediate doses (0.5–1.0 g/kg) was able to reverse the reduction in social exploration induced by caffeine (15.0–30.0 mg/kg). Although there was no interaction between ethanol and CPT or MSX-3 on social exploration in the first day, MSX-3 blocked the amnestic effects of ethanol observed on the following day. Thus, ethanol impairs the formation of social memories, and A2A adenosine antagonists can prevent the amnestic effects of ethanol, so that animals can recognize familiar conspecifics. On the other hand, ethanol can counteract the social withdrawal induced by caffeine, a non-selective adenosine A1/A2A receptor antagonist. These results show the complex set of interactions between ethanol and caffeine, some of which could be the result of the opposing effects they have in modulating the adenosine system.
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