著者は、博士に感謝します。健太郎長岡（東京農工大学）、有用な議論のための渉飯尾（茨城県）。この研究は、農業・医療科学（IUCAM）との間に茨城大学協力（文部科学省、日本）と健康促進給付（NARO）と農産物・食品の開発に関する研究プロジェクト（農林水産省、日本）によって部分的にサポートされていました。

動物実験は、によって承認され、茨城大学の動物実験委員会と教育文化省、スポーツ、科学、技術（文部科学省）、日本（通知No.71）の両方のガイドラインを満たしました。プロトコルの完全な概要を図1に示されています。 1.装置<ol><li> 、そして「社会的敗北（SD）」ケージ（W×D×（[D]は、高さ[H] = 148ミリメートル×293ミリメートル×143ミリメートルを×奥行き×幅[W]）シングルケージ：ケージの2種類を用意135ミリメートル×320ミリメートル）×H = 220ミリメートル。 </li><li> 図2に示すように 、15円孔（：直径8mm 3×5の行列）とアクリル透明板の分周器（厚さ5mm）を持つ2つの区画にSDケージを分けます。 </li><li>トウヒの木、精製・ダイエット食品ペレット、および飲料水ボトルから作られた木材シェービングチップを入手します。また、紙タオル、マスク、ゴム手袋を得ます。 </li&gt; <li>社会的相互作用試験のために、（Wをグレーのポリ塩化ビニル製のオープンフィールドアリーナ（W×D×H = 40センチ×40センチ×40センチ）、鉄鋼（190グラム）で作られた重量、およびプラスチックの対話ボックスを準備×D×H = 10cm角×13センチメートル; 3ワイヤーメッシュ窓（W×D = 5センチメートル×5センチ）で100g）（ 図3）。 </li><li>動物施設における行動試験室での自動追跡システム：CCDカメラ（;; 1.4 1/3インチCCD、F = 1 2.8〜12ミリメートル）を配置します。少なくとも30分間、試験室の環境にマウスを慣らすために行動試験室でマウスのケージのための適切な棚を置きます。 </li></ol>環境へ2.慣れ<ol><li> 5ヶ月以上古く、動物飼育会社から施設への配信ICR（ICR）マウス：7週齢の雄とのSlcあるオスのC57BL / 6JJmsSlc（B6）マウスを使用してください。 </li><li> 独立して、N（B6マウスの2つのグループを移動させます=施設への各グループの12）。 sCSDSモデルを開発するための積極的なICRマウスと別のグループ（被写体B6マウス）をスクリーニングするための一つのグループ（クリーナーB6マウス）を使用します。 </li><li>彼らの積極的な行動をスクリーニングするために、施設にICRマウス（N = 12）を導入。 </li><li>一定温度（23周り℃）および湿度（40％程度）でハウス12時間の明暗サイクル下で1週間個別に1ケージのマウス（100ルクスの蛍光灯の周りに、8時に点灯）環境にそれらを慣らすためです。マウスは、隣接したマウスの行動によって影響されないようにケージの間に白色のプラスチック板を配置することにより、各ケージを分割します。 </li><li>精製されたダイエット食品のペレットを作成し、浸透水自由摂取を逆転。他の非精製飼料ペレットの成分は変更になる場合がありますので、AIN-93G飼料を使用してください。 </li><li>毎日、マウスの体重、食物摂取（FI）、および水摂取（WI）を測定します。 Bを計算します最初の日からODY体重増加（BWG）。 </li></ol>積極的なICRマウスの3スクリーニング<ol><li> 1週間馴化した後、前述したように、クリーナーB6マウスと3分のトライアル（侵入者; 8週齢）のための住民侵入テストを使用したICRマウス（常駐）をスクリーニング午後（14：00-17：00）収容室で約300ルクスの照明下で。 <ol><li>具体的には、ICRマウスは侵入者に対して高い攻撃性を示しているかを調べるには、できるだけ多くの異なったB6マウスに向かって5日間連続して1日3件の試験（合計15試験）のために、各ICRマウスをテストします。試験中、積極的な行動（攻撃かむと急速な動き）の攻撃待ち時間と所要時間を記録します。 </li></ol></li><li>各試験の後、B6、侵入者マウスのダメージの傷をチェックすることにより、超攻撃的なICRマウスを識別します。 </li><li>攻撃待ち時間が侵略スコアの最初のインデックスとして30秒未満である試験の比率を計算します。 </li><li> C言語攻撃待ち時間が侵略スコアの第2の指標として3分未満である試験の比率をalculate。 </li><li>最初のインデックスからの侵略スコアを評価します。最初のインデックスが等しい場合に、第2のインデックスを使用してください。 </li><li>積極的なICRマウスなどの超攻撃的な行動せずに高い攻撃性スコアを持っていたICRマウスを選択します。生後約12ヶ月までの実験の次のセット全体で繰り返し攻撃的なICRマウスを使用します。 ICRマウスの攻撃性を確認するために、すべての実験の前に、上述したようしかし、積極的なICRマウスのスクリーニング処理を行います。 </li><li>スクリーニングの各セッションの後、クリーナーB6マウスの損傷の程度を記録します。マウスが負傷している場合、単一のケージにマウスを分離し、その体重増加、食物摂取および水摂取量をチェックすることによって、進行状況を観察します。マウスでの生理機能や行動に影響を与える深刻な傷の場合は、ローカルIに応じてそれらを安楽死させますACUCガイドライン。 </li></ol> 4. sCSDS <ol><li>環境にそれらを慣らすために単一のケージに個別に初期応力露光（1日目）と家の一日7日（日-6）の前に、マウスを対象B6マウスを紹介​​します。 </li><li>三日（日-2上）1日目の前に、マウスは（SDケージに対象B6の同じ番号を自分の領土を確立させるためにアクリル分割器によって分割された各SDケージのコンパートメントに積極的なICRマウスを移動マウス）。 </li><li>前述のシングルケージ条件のように、白色の仕切り板を使用して、SDケージを分割します。 </li><li>非ストレスコントロールB6マウスの場合は、ペアでマウスを維持するために、SDケージ（マウスの半数）を調製し; 10日間のSDケージに分割器によって分割された各区画内に2匹のマウスを置きます。 </li><li> 1日目に毎日BWG、FI、およびWI測定した後、AFTEのSDケージのコンパートメント（居住者のホームケージ）の1つに場所対象B6マウスrnoon（14：00-16：00）収容室で約300ルクスの照明下では、住民侵入テストを完了するために、最初の攻撃の一口からの物理的な接触時間を測定します。 </li><li> 1日目に、最初の攻撃のbiteから5分に物理的な接触時間を設定し、オブザーバーはMiczek らによって記載されているようにバックまたは相手の脇腹に優先的に向けられているICRマウスによる攻撃に刺されの数をカウントしている。20 B6マウスに物理的ストレスの程度を決定します。 </li><li>物理的な接触時間の後、救助対象B6マウス、およびそれらの毛皮の状態や傷を確認し、記録します。次に、物理的なストレスへの暴露次の日まで、次のSDケージ内のICRマウスに別の区画にB6マウスを置きます。 </li><li> SDケージにアクリル除算器が透明であり、穴が含まれているため、隣接区画に分けるにICRマウスからの視覚、聴覚など、さまざまな感情的なストレス、および嗅覚刺激を受けるB6マウスを公開24時間毎日のためのSDケージのメンター。 </li><li>日常管理のB6マウスのBWG、FI、およびWIを測定した後、1日間のSDケージに各区画に入れます。 </li><li> 2日目に、BWG、FI、およびWIの毎日測定した後、物理的ストレスにそれらを公開するために、他のICRマウスの領土に対象B6マウスをご紹介します。 </li><li> 2日目の最初の攻撃biteから4.5分で物理的な接触の期間を設定し、攻撃刺されの数を数えます。 </li><li>別の区画にコントロールB6マウスを移動し、毎日のペアの配置とパートナーをシャッフルするために、ペアの組み合わせを変更します。 </li><li> 10日目の期間は、最初の攻撃biteから0.5分に設定されているように、一日あたり0.5分までに物理的な接触時間を減らします。 </li><li> 7日目に、SDケージ内のすべての区分に木屑の約半分を交換してください。 </li><li> 10日目の最後​​の物理的なストレスに曝露した後、シングルケージに対象B6マウスを移動。対象B6マウスと同様に、10日目に単一のケージにコントロールB6マウスを移動します。 </li><li> ICRマウスは1〜10日の各試験で5分まで、あらゆる攻撃に刺されが表示されない場合は、裁判を終了します。予備の積極的なICRマウスとICRマウスを交換して、対象のB6マウスのための代替トライアルを実施しています。 </li><li>マウスが負傷している場合、単一のケージにマウスを分離し、その体重増加、食物摂取および水摂取量をチェックすることによって、進行状況を観察します。鎮痛のためのあなたのIACUCのガイドラインに従ってください。マウスでの生理機能や行動に影響を与える深刻な傷の場合には、地元のIACUCガイドラインに従って、それらを安楽死させます。 </li></ol> 5.社会的回避試験（社会的相互作用試験） <ol><li> 11日目（00：00-12 09）朝の社会回避のための行動テストを実行します。 </li><li>試験前の30分、行動に棚（1未満ルクスの薄暗い光）に制御し、対象B6マウスのケージを転送20未満ルクスの照明下で、試験室は、彼らが環境に慣らすようにします。 </li><li>オーダー影響を低減するために、交互に制御し、対象のB6マウスをテストします。 </li><li> （フィールドの中央で20ルクスの光で照明）オープンフィールドアリーナ、各マウスは糞、尿を除去するための行動試験の前に70％エタノールを浸したペーパータオルを使用して、プラスチック製の対話ボックス、および任意の臭いをきれいに。 </li><li>オープンフィールド装置の近くに単一のケージから（侵略者として使用されていない）見慣れないICRマウスを置きます。 </li><li> 図4に示すように、空いている相互作用ボックスのオープンフィールドにB6マウスを置きます。（ステップ5.10で説明）自動解析システムを用いて2.5分間の行動を監視し、分析します。 </li><li>最初の試験の後、フィールドからB6マウスを削除し、そのホームケージにそれを置きます。 </li><li>これに続いて、対話ボックスに不慣れの雄性ICRマウス（社会的目標）を配置し、B6を紹介マウスのオープンフィールドに、2.5分間、その動作を監視します。 </li><li>二審の後、ホームケージにB6とICRマウスの両方を返し、上記のようにフィールドとの相互作用ボックスを清掃してください。 </li><li>その社会的な動作をテストするために、各B6マウスにこれらの手順を繰り返します。各試行の間に、CCDカメラを用いたトップビュームービーを記録します。 <ol><li>行動試験の後に、後藤ら 13に示すように、各試験のために（秒）と（秒）の隅領 ​​域に相互作用ゾーンにおいて費やした時間を計算します。マウスの中央に基づいて、マウスの位置を判断します。 </li><li>クリシュナンらに発表された方法に従って、（標的との相互作用時間）×100として社会的相互作用スコアを計算/（ターゲットのない相互作用時間）。21。 </li></ol></li></ol>

<ol>
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L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurobiological+sequelae+of+witnessing+stressful+events+in+adult+mice.">Neurobiological sequelae of witnessing stressful events in adult mice.</a> Biol. Psychiatry. 73 (1), 7-14 (2013).</li><li>Savignac, H. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+sensitivity+to+the+effects+of+chronic+social+defeat+stress+in+an+innately+anxious+mouse+strain.">Increased sensitivity to the effects of chronic social defeat stress in an innately anxious mouse strain.</a> Neuroscience. 192, 524-536 (2011).</li><li>Green, J. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Childhood+Adversities+and+Adult+Psychiatric+Disorders+in+the+National+Comorbidity+Survey+Replication+I:+associations+with+first+onset+of+DSM-IV+disorders.">Childhood Adversities and Adult Psychiatric Disorders in the National Comorbidity Survey Replication I: associations with first onset of DSM-IV disorders.</a> Arch. Gen. Psychiatry. 67 (2), 113-123 (2010).</li><li>Miniati, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+characteristics+and+treatment+outcome+of+depression+in+patients+with+and+without+a+history+of+emotional+and+physical+abuse.">Clinical characteristics and treatment outcome of depression in patients with and without a history of emotional and physical abuse.</a> J. Psychiatr. Res. 44 (5), 302-309 (2010).</li><li>Tao, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Examining+the+relationship+between+lifetime+stressful+life+events+and+the+onset+of+major+depression+in+Chinese+women.">Examining the relationship between lifetime stressful life events and the onset of major depression in Chinese women.</a> J. Affect. Disord. 135 (1-3), 95-99 (2011).</li><li>Valente, S., Fisher, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recognizing+and+managing+psychogenic+polydipsia+in+mental+health.">Recognizing and managing psychogenic polydipsia in mental health.</a> J. Nurse Pract. 6 (7), 546-550 (2010).</li><li>Dundas, B., Harris, M., Narasimham, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychogenic+Polydipsia+Review:+Etiology,+Differential,+and+Treatment.">Psychogenic Polydipsia Review: Etiology, Differential, and Treatment.</a> Curr. Psychiatry Rep. 9 (3), 236-241 (2007).</li><li>Tsumura, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Downregulation+of+AQP2+expression+in+the+kidney+of+polydipsic+STR/N+mice.">Downregulation of AQP2 expression in the kidney of polydipsic STR/N mice.</a> Am. J. Physiol. Renal Physiol. 290 (2), F478-F485 (2006).</li><li>Flores, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Schedule-Induced+Polydipsia:+Searching+for+the+Endophenotype+of+Compulsive+Behavior.">Schedule-Induced Polydipsia: Searching for the Endophenotype of Compulsive Behavior.</a> World J. Neurosci. 4, 253-260 (2014).</li><li>Cryan, J. F., Dinan, T. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mind-altering+microorganisms:+the+impact+of+the+gut+microbiota+on+brain+and+and+behaviour.">Mind-altering microorganisms: the impact of the gut microbiota on brain and and behaviour.</a> Nat. Rev. Neurosci. 13 (10), 701-712 (2012).</li></ol>

著者は、彼らが競合する金融利害関係を有していないことを宣言します。

標準CSDSプロトコル19（日あたりの侵略との物理的接触の5〜10分）にかけsCSDSマウスとCSDSのマウスとの間の体重の決定的な差がありました。標準CSDSマウスは、ストレス期間21,22,23の間に体重の減少を示したsCSDSマウスは、ストレス期間中BWGの増加を示しました。 10日間のストレス期間中の侵略者との物理的接触の全持続時間の点で、2つのプロトコル間の実質的な違いがあります...

ストレスの多いイベントの多くの種類は、人間の生涯を通じて発生します。過度のストレスは、多くの場合、ヒトおよび動物における有害な生理学的結果につながります。ヒトでは、ストレスの多い出来事は、うつ病などの精神障害1を沈殿させるための主要な危険因子です。疾患研究の世界的負担は、うつ病は障害2と住んでいた障害調整生存年数（DALYs）と年の点で最も無効疾患の一つであることが示されました。また、うつ病は自殺DALYs 3の最も大きな割合を占めています。うつ病に苦しんでいる人々は、それが難しい自分たちの生活を管理するために見つけ、その結果、生活の質がしばしば悪化します。したがって、これらの患者の生活の質を改善するために効果的な治療法を開発する強い必要性が存在します。 多くの研究は、大うつ病性障害に対して実行されており、疾患に対する遺伝的寄与ことを明らかにしたsusceptibilityは小さな効果4の複数の遺伝子座の効果によって説明されて約30〜40％です。そのため、うつ病の根底にある複雑な病原性のメカニズムの、疾患の詳細な病因は、とらえどころのないまま。臨床報告は減少し、体重増加を示し、このようなメランコリーおよび非定型うつ病5とうつ病のサブタイプは、それぞれ6が存在することを示しています。 25〜30％とうつ病の患者15〜30％が純粋なメランコリーと非定型の特徴を表しているが、それぞれ、それらのほとんどは、両方のサブタイプ7の混合機能を備えています。そのため、大うつ病は症状の広い範囲を持っています。バイオマーカーを発見し、ヒトにおけるうつ病の様々なタイプの客観的治療薬を開発するためには、うつ病8のいくつかの異なる動物モデルを確立することが重要です。 うつ病の動物モデルを学習を含むいくつかのアプローチを使用して確立されています無力感、慢性予測不可能な軽度のストレス、および慢性社会的敗北ストレス（CSDS）9-12。豊田らは、うつ病に関連付けられている代謝や行動を解明するために、ラットとマウス13-17のCSDSモデルを確立しました。うつ病の動物モデルは、顔の有効性18によって評価されることを考えると、モデルが確立されているコンテキストが重要です。また、ゴールデンら 19は、詳細にCSDSマウスを作成するための方法を報告しました。これは、CSDSマウスの社会的行動の欠損は、慢性治療により回復し、なく抗うつ薬での急性治療によって、それらは脳由来神経栄養性の調節の観点からうつ病を有する患者のものと類似した症状を共有することができることが知られています因子 6。 後藤ら 13は、以前の方法を変更することにより、亜慢性および軽度の社会的敗北ストレス（sCSDS）マウスモデルを開発しましたゴールデンら 19。 sCSDSマウスは体重増加と体水分量13の利益以下polydipsia-と過食症に似た症状を示します。このレポートでは、sCSDSマウスモデルを確立するためのプロトコルが提供されており、我々はこのモデルの有用性を議論します。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>single cage</td>
			<td>Charles River Laboratories Japan</td>
			<td></td>
			<td>width [W] &#215; depth [D] &#215; height [H] = 143 &#215; 293 &#215; 148 mm</td>
		</tr>
		<tr>
			<td>M cage</td>
			<td>Natsume Seisakusho</td>
			<td></td>
			<td>W &#215; D &#215; H = 220 &#215; 320 &#215; 135 mm</td>
		</tr>
		<tr>
			<td>Whiteflake</td>
			<td>Charles River Laboratories Japan</td>
			<td></td>
			<td>Wood-shaving chips made from spruce trees</td>
		</tr>
		<tr>
			<td>AIN-93G</td>
			<td>Oriental Yeast</td>
			<td></td>
			<td>purified-diet food pellets</td>
		</tr>
		<tr>
			<td>Kimtowel</td>
			<td>Nippon Paper Crecia Co.</td>
			<td></td>
			<td>Paper towels</td>
		</tr>
		<tr>
			<td>open-field arena</td>
			<td>O&#8217;Hara &#38; Co.</td>
			<td></td>
			<td>made of gray polyvinylchloride</td>
		</tr>
	</tbody>
</table>

a mouse model of subchronic and mild social defeat stress for understanding stress-induced behavioral and physiological deficits

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of depression is essential. Because there are several types of depression, various animal models are needed for a deeper understanding of the disorder. Previously, a mouse model of subchronic and mild social defeat stress (sCSDS) using a modified chronic social defeat stress (CSDS) paradigm was established. In the paradigm, to reduce physical injuries from aggressors, the duration of physical contact between the aggressor and a subordinate was reduced compared to in the original CSDS paradigm. sCSDS mice showed increased body weight gain, food intake, and water intake during the stress period, and their social behaviors were suppressed after the stress period. In terms of the face validity of the stress-induced overeating and overdrinking following the increased body weight gain, the sCSDS mice may show some features related to atypical depression in humans. Thus, a mouse model of sCSDS may be useful for studying the pathogenic mechanisms underlying depression. This protocol will help establish the sCSDS mouse model, especially for studying the mechanisms underlying stress-induced weight gain and polydipsia- and hyperphagia-like symptoms.

10日間の期間にわたってのための物理的ストレスの程度を監視するには、ICRマウスによる攻撃に刺されの数を手動で研究者によってカウントした。 図5（a）は、受信攻撃刺さ数の個々の値を示しています。そこ早期（1日目に約10〜120刺さ）にはかなりのばらつきがあったが、この変動は、後の段階（10日目に約5-20刺さ）に減少した。 図5（b）は、攻撃刺されの平均数...

Watch this Scientific Journal Video about A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits at JoVE.com

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

ここでは、亜慢性軽度ソーシャル敗北ストレスのマウスモデルを開発するための方法が記載され、体重増加、以下hyperphagia-および多渇症様症状を含むうつ病の病原性の特徴を調べるために使用されます。

ストレスによって誘発される行動や生理障害を理解するための亜慢性マイルド社会敗北ストレスのマウスモデル

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of ...

a-mouse-model-subchronic-mild-social-defeat-stress-for-understanding

Research

JoVE Journal

Behavior

19.4K ビュー.  Ibaraki University. ここでは、亜慢性軽度ソーシャル敗北ストレスのマウスモデルを開発するための方法が記載され、体重増加、以下hyperphagia-および多渇症様症状を含むうつ病の病原性の特徴を調べるために使用されます。 

ビデオ: A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.

This video shows the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression, defensive behavior and violence in a semi-natural setting. The use of the paradigm for social stress experiments is explained as well.

レジデント·侵入者パラダイム：攻撃的、暴力と社会的ストレスのために標準化されたテスト

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to ...

行動学

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.

This article describes the use of chronic resident intruder social stress as an ethologically relevant paradigm to model postpartum depression and anxiety in lactating rodents.

げっ歯類の授乳でモデル産後うつ病への慢性的社会的ストレスを使用

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

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.

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.

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

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several ...

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

トリーアの社会ストレステストにおけるソーシャルサポートと社会的アイデンティティの実験操作：ストレスの社会的側面

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.g., hypercortisolemia, hypertension) and neurological (e.g., anhedonia, learned helplessness) changes that are clinically associated with depression. Importantly, UCMS-induced depressive symptoms can be ameliorated through chronic, but not acute, treatment with common SSRIs. As such, the UCMS protocol offers many advantages over acute stress protocols or protocols that utilize more extreme stressors. Our protocol involves randomized, daily exposures to 7 distinct stressors: damp bedding, removal of bedding, cage tilt, alteration of light/dark cycles, social stresses, shallow water bath, and predator sounds/smells. By subjecting rodents 3-4 hr daily to these mild stressors for 8 weeks, we demonstrate both significant behavioral changes and poor health outcomes to the cardiovascular system. This approach allows for in-depth interrogation of the neurological, behavioral, and physiological alterations associated with chronic stress-induced depression, as well as for testing of new potential therapeutic agents or intervention strategies.

The unpredictable chronic mild stress (UCMS) protocol is a validated method for studying behavioral and physiological changes associated with chronic stress and depressive symptoms. Eight weeks of imposition of the UCMS protocol induces behavioral changes and poor health outcomes in rodents of either gender.

げっ歯類での抑うつ症状を扇動、行動の変化と負の健康アウトカムのための予測不可能な慢性的な軽度のストレスプロトコル

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

外傷性脳損傷後のラットの行動の赤字を検出

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

マウスで無快感を誘導するため予測不可能な慢性的な軽度ストレス プロトコル

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders such as post-traumatic stress disorder (PTSD). To understand the biological mechanisms of fear dysregulation in PTSD, it is important to start with a valid animal model of the disorder. This protocol describes the methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of PTSD, in both rats and mice. SEFL was developed to recapitulate critical aspects of PTSD, including long-term sensitization of fear learning caused by an acute stressor. SEFL uses aspects of Pavlovian fear conditioning but produces a distinct and robust sensitized fear response far greater than normal conditional fear responses. The trauma procedure involves placing a rodent in a conditioning chamber and administering 15 unsignaled shocks randomly distributed over 90 minutes (for rat experiments; for mouse experiments, 10 unsignaled shocks randomly distributed over 60 minutes are used). On day 2, rodents are placed in a novel conditioning context where they receive a single shock; then, on day 3 they are placed back in the same context as on day 2 and tested for changes in freezing levels. Rodents that previously received the trauma display enhanced levels of freezing on the test day compared to those that received no shocks on the first day. Thus, with this model, a single highly stressful experience (the trauma) produces extreme fear of the stimuli associated with the traumatic event.

Here we describe the detailed methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of post-traumatic stress disorder, in both rats and mice. The model utilizes aspects of Pavlovian fear conditioning and freezing as an index of enhanced fear in rodents.

恐怖のストレス強化学習、心的外傷後ストレス障害の堅牢な齧歯動物モデル

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders ...

A Visual Guide for Studying Behavioral Defenses to Pathogen Attacks in Leaf-Cutting Ants

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies have described the behaviors connected with disease defense, and the associated use of chemicals and antimicrobials, no common visual reference has been made. The main aim of this study was to record short clips of behaviors involved in disease defense, both prophylactically and directly targeted towards an antagonist of the colony following infection. To do so we used an infection experiment, with sub-colonies of the leaf-cutting ant species Acromyrmex echinatior, and the most significant known pathogenic threat to the ants&#39; fungal crop (Leucoagaricus gongylophorus), a specialized pathogenic fungus in the genus Escovopsis. We filmed and compared infected and uninfected colonies, at both early and more advanced stages of infection. We quantified key defensive behaviors across treatments and show that the behavioral response to pathogen attack likely varies between different castes of worker ants, and between early and late detection of a threat. Based on these recordings we have made a library of behavioral clips, accompanied by definitions of the main individual defensive behaviors. We anticipate that such a guide can provide a common frame of reference for other researchers working in this field, to recognize and study these behaviors, and also provide greater scope for comparing different studies to ultimately help better understand the role these behaviors play in disease defense.

We present a visual guide to disease defense behaviors in leaf-cutting ants, with individual clips and accompanying definitions, illustrated in an experimental infection scenario. Our main aim is to help other researchers recognize key defensive behaviors and to provide a common understanding for future research in this field.

病原体の防御行動を研究するための視覚的なガイドの剪葉アリの攻撃します。

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies ...

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.&#160;

Here, we present a protocol to quantify nest building behavior in mice, which is known to be impaired in several neurological disorders and diseases. This protocol examines the utility of four materials and offers the opportunity to quantify the rater agreement in scoring, improving the validity and reliability of the assay.