Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior.

Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior.
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DOI:
10.1016/j.neuroscience.2015.08.052
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发表时间:
2015-10-29
期刊:
影响因子:
3.3
通讯作者:
Veenema AH
Veenema AH
中科院分区:
医学3区
文献类型:
--
作者:
Bredewold R;Schiavo JK;van der Hart M;Verreij M;Veenema AH

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社交游戏是一种有动机且有益的行为,几乎所有哺乳动物都会表现出这种行为,并在幼年时期达到顶峰。此外,社交游戏对于社交技能的发展至关重要,但在自闭症等社交障碍中会受到损害。我们最近表明,侧隔膜(LS)参与幼年雄性和雌性大鼠社交游戏行为的调节。 LS 很大程度上受 GABA 和谷氨酸神经传递的调节,但它们在社交游戏行为中的作用尚不清楚。在这里,我们确定了社交游戏行为是否与 LS 中 GABA 和谷氨酸的细胞外释放变化有关,以及这些变化在多大程度上调节雄性和雌性幼年大鼠的社交游戏行为。在自由行为的大鼠中使用脑内微透析,我们发现细胞外 GABA 浓度没有性别差异,但在基线条件和社交游戏期间,雄性的细胞外谷氨酸浓度高于雌性。这导致男性的谷氨酸/GABA 浓度比高于女性,因此男性的 LS 具有兴奋性优势。此外,两性的社交游戏行为都与 LS 中 GABA 和谷氨酸的细胞外释放显着增加有关。荷包牡丹碱(100 ng/0.5 µl、250 ng/0.5 µl)对 LS 中 GABA-A 受体的药理学阻断会剂量依赖性地减少两性社交游戏行为的持续时间。相比之下,用 AP-5 + CNQX(2 mM+0.4 mM/0.5 µl、30 mM+3 mM/0.5 µl)对 LS 中的离子型谷氨酸受体(NMDA 和 AMPA/红藻氨酸受体)进行药物阻断,剂量依赖性地减少了女性社交游戏行为的持续时间,但没有改变男性社交游戏行为。总之,这些数据表明,LS 中的 GABA 神经传递在两性青少年社交游戏行为的调节中发挥着作用,而 LS 中的谷氨酸神经传递则参与青少年社交游戏行为的性别特异性调节。
Social play is a motivated and rewarding behavior that is displayed by nearly all mammals and peaks in the juvenile period. Moreover, social play is essential for the development of social skills and is impaired in social disorders like autism. We recently showed that the lateral septum (LS) is involved in the regulation of social play behavior in juvenile male and female rats. The LS is largely modulated by GABA and glutamate neurotransmission, but their role in social play behavior is unknown. Here, we determined whether social play behavior is associated with changes in the extracellular release of GABA and glutamate in the LS and to what extent such changes modulate social play behavior in male and female juvenile rats. Using intracerebral microdialysis in freely behaving rats, we found no sex difference in extracellular GABA concentrations, but extracellular glutamate concentrations are higher in males than in females under baseline condition and during social play. This resulted in a higher glutamate/GABA concentration ratio in males versus females and thus, an excitatory predominance in the LS of males. Furthermore, social play behavior in both sexes is associated with significant increases in extracellular release of GABA and glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with bicuculline (100 ng/0.5 µl, 250 ng/0.5 µl) dose-dependently decreased the duration of social play behavior in both sexes. In contrast, pharmacological blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in the LS with AP-5 + CNQX (2 mM+0.4 mM/0.5 µl, 30 mM+3 mM/0.5 µl) dose-dependently decreased the duration of social play behavior in females, but did not alter social play behavior in males. Together, these data suggest a role for GABA neurotransmission in the LS in the regulation of juvenile social play behavior in both sexes, while glutamate neurotransmission in the LS is involved in the sex-specific regulation of juvenile social play behavior.