Summary

適度な出生前アルコール暴露と成体ラットにおける社会行動の定量化

Published: December 14, 2014
doi:

Summary

The goal of the protocol presented here is to describe procedures to expose rats to moderate levels of alcohol during prenatal brain development and to quantify resulting alterations in social behavior during adulthood.

Abstract

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Introduction

子供の推定1から5パーセントは、胎児性アルコール症候群(FAS)、部分的なFAS(PFAS)、およびアルコール関連神経発達障害(ARNDs)3、胎児性アルコールスペクトラム障害(FASDs)2、と診断されている。社会的行動と認知の赤字はFASDs 4-7の小児において観察された最も一般的な有害転帰の一つです。否定的な結果が重い出生前のアルコール暴露(PAE)に限定されないが、目立った形態学的にはつながらない適度なPAEとして、FASの行動および認知障害特性FASDs 8-10ヒトにおける、比較的微妙な、しかしそれにもかかわらず、永続的な障害を引き起こす可能性非ヒト動物は、脳の発達11中のエタノールに曝露した。適度なPAEの行動と対応する神経生物学的影響を理解することの重要性は、現在の見積りによって強調されるFASD症例の大多数は少ない秒内に収まることを示すスペクトル12のエヴェーレ範囲。

いくつかの独立した研究室は、社会的な刺激に、17,18の応答性の変化を積極的な相互作用を増加し、調査と相互作用1,13-15変更されたプレイ14,16,17を含む、脳の発達の間に露出をエタノールに関連する齧歯類社会的行動の変化を報告している19-21、そして社会的に獲得した食べ物の好みと社会的認識メモリ22の欠損。社会的行動の赤字が重い(血中エタノール濃度(BECは)〜300mgの/ DL)22,23またはエタノールのより緩やかなレベル(BECを〜80mgの/ DL)1、および他の重要なパラメータの幅広い以下の露出を観察されている行動測定時の露光タイミング、曝露期間、年齢などの要因。

これまでの研究では、社会的なint型の特定の側面でその変化を実証した成人期におけるeractionは1,18サッカリンに暴露された対照動物からのアルコールの適度なレベルに暴露されたラットを区別する。成人期に(相手のスニッフィング、 例えば )具体的には、適度なPAEは一貫して積極的な行動の増加を示唆している、レスリングで堅牢な増加と関連している、と社会調査のより低いレベル。社会的行動の変化は、PAEの信頼性のある結果であるため、PAE以下の社会的行動の定量化は、社会的行動におけるPAE関連の変化の神経基盤のより完全な理解とインターベンショナルアプローチの開発に向けて進んための重要性を保持することができる。この論文と関連するビデオの目標は、中程度のPAEプロトコルと確実に区別出生前非露光ラットの子孫からアルコールに露出している大人の子孫における社会的行動の定量化のための方法に命令を提供することです。

Protocol

ここ及び添付のビデオで説明したすべての手順は健康科学センターとニューメキシコ大学のメインキャンパスの施設内動物管理使用委員会によって承認されている。 1.出生前エタノール曝露サッカリンナトリウム塩水和物、190プルーフのエタノール(体積95%のアルコール)、ビーズのガラス飲料チューブ、天然ゴム白#4ストッパー1ホール、1「ベンドチューブ?…

Representative Results

多くの繁殖ラウンドの過程でエタノール状態の雌ラットは、一貫して4時間の飲み会あたりのエタノールの約2.1グラム/ kgの平均を飲む。ラットダムは45分の時点で測定された約60mg / dlのピーク母体血清中のエタノール濃度が、結果として、飲料チューブを導入した後の最初の15〜30分の間に4時間の合計の約半分を消費する。飲酒期間の残りの3.5時間かけて、それらは0.4グラム/ kg体重/時間の下?…

Discussion

ここで説明する出生前のアルコール暴露パラダイムは、妊娠中のラットダムによるエタノールの自主的な消費を(5%v / v)を伴う。エタノール投与のタイミング、投与量、持続時間および経路に関してならびに研究中の種と異なり、文献に示される脳の発達中にエタノールに非ヒト動物を露出させるための多くのプロトコルが存在する。種々の露光プロトコルの利点の完全な治療がここで提?…

Divulgations

The authors have nothing to disclose.

Acknowledgements

Support provided by grant AA019462 to DAH and AA019884 to DDS.

Materials

Saccharin sodium salt hydrate Sigma S1002
190 proof ethanol Sigma 493538
Beaded glass drinking tubes Fisher 14-955K
Natural rubber white #4 stopper one hole Plasticoid LSG4M181
1" bend tubes-ball point Ancare TD-199-3"
Paper rulers N/A N/A www.vendian.org/mncharity/dir3/paper_rulers
Apparatus for social interaction Custom built N/A 95 cm X 47 cm X 43 cm
Video cameras N/A N/A Capable of recording low/no light conditions
Infrared illuminators Vitek VT-IR1-12
Teklad laboratory grade sani-chips Harlan 7090A
Brush and dustpan N/A N/A
Isopropyl alcohol Sigma W292907
Chlorine Dioxide (1.5 mg Tablets) Quiplabs N/A Prepare per manufacturer's recommendation

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Hamilton, D. A., Magcalas, C. M., Barto, D., Bird, C. W., Rodriguez, C. I., Fink, B. C., Pellis, S. M., Davies, S., Savage, D. D. Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats. J. Vis. Exp. (94), e52407, doi:10.3791/52407 (2014).

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