幼鼠社交玩耍行为期间外侧隔区γ-氨基丁酸（GABA）和谷氨酸细胞外释放的动态变化：对社交玩耍行为性别特异性调节的意义
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.
作者信息
Bredewold R, Schiavo J K, van der Hart M, Verreij M, Veenema A H
机构信息
Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA.
Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA.
出版信息
Neuroscience. 2015 Oct 29;307:117-27. doi: 10.1016/j.neuroscience.2015.08.052. Epub 2015 Aug 28.
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 conditions and during social play. This resulted in a higher glutamate/GABA concentration ratio in males vs. 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 (2mM+0.4mM/0.5 μl, 30 mM+3mM/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.
社交玩耍是一种有动机且能带来回报的行为，几乎所有哺乳动物都会表现出这种行为，并且在幼年期达到高峰。此外，社交玩耍对于社交技能的发展至关重要，在自闭症等社交障碍中会受到损害。我们最近发现，外侧隔区（LS）参与调节幼年雄性和雌性大鼠的社交玩耍行为。LS主要受γ-氨基丁酸（GABA）和谷氨酸神经传递的调节，但其在社交玩耍行为中的作用尚不清楚。在此，我们确定社交玩耍行为是否与LS中GABA和谷氨酸的细胞外释放变化相关，以及这种变化在多大程度上调节幼年雄性和雌性大鼠的社交玩耍行为。通过对自由活动的大鼠进行脑内微透析，我们发现细胞外GABA浓度不存在性别差异，但在基线条件下和社交玩耍期间，雄性大鼠的细胞外谷氨酸浓度高于雌性大鼠。这导致雄性大鼠与雌性大鼠相比，谷氨酸/GABA浓度比值更高，因此，雄性大鼠的LS中存在兴奋性优势。此外，两性的社交玩耍行为都与LS中GABA和谷氨酸的细胞外释放显著增加有关。用荷包牡丹碱（100 ng/0.5 μl，250 ng/0.5 μl）对LS中的GABA-A受体进行药理学阻断，剂量依赖性地缩短了两性的社交玩耍行为持续时间。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/海人藻酸受体）进行药理学阻断，剂量依赖性地缩短了雌性大鼠的社交玩耍行为持续时间，但对雄性大鼠的社交玩耍行为没有影响。总之，这些数据表明，LS中的GABA神经传递在调节两性幼年社交玩耍行为中起作用，而LS中的谷氨酸神经传递参与幼年社交玩耍行为的性别特异性调节。
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