This work was funded by the University of Michigan Department Of Psychiatry (U032826; JDM), the National Institute on Drug Abuse (NIDA; K08 DA037912-01; JDM) and the Department of Defense (DoD) National Defense Science and Engineering Graduate (NDSEG) Fellowship (CJF).

（;ミシガン大学、ミシガン州アナーバーUCUCA）すべての手順は、大学動物の使用およびケアに関する委員会によって承認されています。 1.機器とソフトウェア<ol><li>商業オペラントチャンバーとデバイスを取得します。 材料 表を参照してください 。 </li><li>ラットオペラント条件付けチャンバ内で周囲の雑音を提供するために、換気ファンと音減衰キャビネットに位置し、（20.5センチメートル深さX 29.2センチメートル×高さ24.1センチメートル幅）研修を実施。 </li><li> 3センチメートルステンレス鋼格子床以上のオペラントチャンバー21.6センチ前壁の中央に位置し、ペレット誌（レセプタクル）との各チャンバを、装備。ペレットマガジンが装置内にヘッドエントリを検出することができる赤外線センサーが含まれていることを確認してください。 </li><li>バナナ風味の食物ペレット（45 mg）を提供ペレットディスペンサーにペレット雑誌を接続します。 </li><li>カウンターバランスの取れた方法で、位置1リトラクタブルル版（CS）、ペレット容器の両側に約2.5センチ3センチメートルステンレス鋼格子床の上（左または右）。 </li><li>レバーが拡張されたレバーをより視覚的に目立つ作るために、その中にLED合図灯が含まれていることを確認してください。 </li><li>リトラクタブルレバーを使用している場合は、レバーの上に10グラムの校正用分銅を配置し、その後、それだけで重量が押下できるようになるまで六角ナットレンチで（デバイスの上部に位置）の校正ネジを調整することにより、レバーをキャリブレーションレバー。 </li><li>雑誌のレセプタクル反対側の壁上室の上部にある赤い家ライトを装備。 注：赤家光が照射さレバーの目立ちを増加させるために使用されます。 </li></ol> 2. PCAトレーニング<ol><li>ペア社内の大人の雄Sprague Dawleyラット（250〜300グラム）到着時と12時間の明/暗サイクルで維持されている住宅地、中に少なくとも2日間、邪魔されずにそれらを残します。 </li><li>静かにEAを扱います人間との接触にラットを順応させるために2日間一日あたり少なくとも1分間chのラット。住宅地での食料と水をラットに自由摂取のアクセスを提供します。 </li><li> PCAの訓練に3日前に開始し、2日間のために彼らのホームケージに（ラット当たり約15ペレット）食物ペレットを配置することにより、バナナ風味の食物ペレットのラットを習熟。 注意：ラットをペアに収容されている場合は、ホームケージの両側に均等にペレットを分割することは有用です。 </li><li>事前訓練プログラム 注意：私たちのプログラミングのすべてが（メッドアソシエイツ、ソフトウェア用）MEDState表記を使用して行われ、マニュアルはオンラインで入手可能（mednr.com/pdf/doc003_MedPCProgramr.pdf）です。プログラムが適切な拡張子で保存MedState記法使用してフォーマットされていないテキスト文書（ 例えば 、ASCIIまたはDOSテキスト）、として書かれている（ すなわち 、[ファイル名] .mpc）、その後、MED-PCプログラム、トランスIVを使用して翻訳。これらの工程の全ては、上記プロでより詳細に提供されていますマニュアルをグラミング。 <ol><li> 5分のプログラム（ すなわち、1食のペレットは平均30秒ごとに配信され開始後の可変時間に50食のペレット（VT）30秒スケジュールを配信する事前訓練プログラムを作成しますが、実際の配信は0-の間でランダムに変化60秒）。 </li><li>赤い家の光が上になるように事前訓練プログラムを書くが、レバーは（約25分）プログラムの期間引っ込めたまま。 </li><li>光サイクルの間に事前訓練と後続のすべての実験を行います。 </li><li>ある日、PCAのトレーニング、オペラントチャンバー内に各ラットを置き、近くに先立って、チャンバのドアをラッチし、音減衰キャビネットドアを閉じます。 </li><li>そのチャンバー内で各ラットを配置した後、できるだけ早く事前訓練プログラムを起動します。 </li><li>プログラム終了後できるだけ早くその室から各ラットを削除します。 </li><li>消費ペレットの数を記録し、すべてを消費しないラットを除外さらなる試験からのペレット。 </li></ol></li><li>プログラムの開始後1分を始め、約40分で25件の試験を提供し、PCAのトレーニングプログラムを作成します。 <ol><li>各試験中にレバーがチャンバ内に延長され、8秒間点灯しているように、プログラムを書きます。 </li><li>ペレットマガジンに1食品ペレットの応答に依存しない配信の直後するプログラムレバー後退。 </li><li> VT 90秒のスケジュール上の個別の各試験（ すなわち 、レバーの延長と、その後の食品ペレットの配信は平均で毎90秒に発生しますが、実際の配信は30から150秒の間でランダムに変化）。 </li><li>近くに、コンディショニング室に各ラットを置き、チャンバドアラッチ、および音減衰キャビネットドアを閉じます。 </li><li>そのチャンバー内で各ラットを配置した後、できるだけ早くPCAのトレーニングプログラムを開始します。 </li><li>プログラム終了後できるだけ早くその室から各ラットを削除します。 </li><li> Eさらなる試験からペレットのすべてを消費しないxcludeラット。 </li></ol></li></ol> 3.データ処理<ol><li>スプレッドシート（ 例えば 、スプレッドシート文書）に出 ​​力情報を転送します。 </li><li> （被験者番号開始日、開始時刻、およびボックス番号）情報を識別する抽出するプロファイルを作成だけでなく、出力情報（番号とレバーを押すと雑誌エントリの待ち時間）。 注：実験では、非CSマガジンエントリは、プロファイルによって抽出されます。 8秒CS期間外とレバーが拡張されていない時にVT 90秒（ すなわち 、60から120秒）の期間中に発生した雑誌へのエントリとして非CS雑誌エントリを定義します。 </li><li>さらに8秒でレバーを押すと雑誌エントリの待ち時間をキャップすることによってデータを処理する（ すなわち 、CS提示の持続時間）。これは、IF関数を使用してスプレッドシートで達成することができます：IF（&gt; 8,8 X、X）。 </li><li>スコアを計算、待ち時間スコアレバープレスや雑誌エントリを実行する（ すなわち 、平均待ち時間- ;応答バイアス（/ [レバー押し+雑誌エントリ] [雑誌エントリレバーを押す]セッションのレバーを押すと雑誌のエントリのすなわち 、合計数）のためにセッション中に、[雑誌エントリー待ち時間-レバーを押し待ち時間] / 8）、および確率の差（ すなわち 、レバーを押すか、雑誌のエントリの割合; [レバーを押し確率-雑誌のエントリ確率]）5。 注：これらの式では、すべてのスコアが1.0と-1.0の間の範囲であるべきです。 </li><li>各個別のセッション内でその応答の偏り、待ち時間スコア、および確率差を平均化することによって各ラットのためのPCAインデックススコアを計算します。 注：PCAインデックススコアは1.0と-1.0の間の範囲であるべきです。 </li></ol>

<ol>
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The authors have nothing to disclose.

PCAのトレーニングは、中毒の脆弱性の重要な要素であると主張されてきた馴化手がかりにインセンティブ顕現属性する傾向の個人差を決定するために使用することができます。例えば、以前のSTは、両方の食品や薬の合図6にインセンティブ顕現属性ことが実証されている、と食物と薬物関連の両方の手がかりは、STS 7でへんとう-線条体-視床回路内の類似の脳領域を活性化さ?...

中毒への薬物使用の移行は、パブロフと道具的学習1,2の間の複雑な相互作用を伴います。薬物服用と薬物探索行動の間に、行動と結果は楽器のプロセスを通じて学習されています。しかし、 刺激 （例えば、薬物関連手がかり）と報酬の間の関係もパブロフのプロセスを通じて学習されています。パブロフの手がかりは、予測値を取得し、彼らはまた、インセンティブの動機づけ、彼らは魅力的になることにより、値3、望ましい、と報酬を求める行動4を促進し、維持することができるを取得することができます。 動物の学習報酬を調査する多くの手順は、しかし、インセンティブ動機付け学習対予測の解きほぐしを許可していません。薬物自己投与手順では、例えば、両方の楽器とパブロフの偶発事象は、典型的には、ラットがアクションを実行することを学ぶように、採用されている（ 例えば 、鼻、pokiNG、レバー押しの結果（ すなわち 、静脈内薬物注入）を受信するために） など 。やりがいの結果はまた、パブロフの刺激と対になっている（ 例えば 、鼻突くポート、キューライトプレゼンテーション、輸液ポンプの音、血流への流体送達の内受容性の感覚などの照明）。これは、キューがいうだけの理由で報酬との予測関係の目標指向行動をサポートしているかどうか、またはキューが自分自身のインセンティブ動機付け特性を獲得しているかどうか、これらの手順では、多くの場合不明です。 実験的にパブロフの刺激の予測値からインセンティブ動機付け値を単離するために、私たちの研究室では手がかり関連を報いるためにインセンティブ顕現属性ラットを識別するために、パブロフの条件付けのアプローチ（PCA）の手順を使用しています。トレーニングセッション中に、条件刺激（CS;例えば、レバー）が応答-独立delivを予測無条件刺激（; 例えば 、食品ペレット米国）のERY。複数のトレーニングセッションの間に、3の表現型の開発：サイン・トラッキング（CS指向条件反応[CR]）、目標追跡（米国指向CR）を、中間応答（CRの両方）。目標トラッカー（GTS）は、CSが報酬配信の予測因子として利用されています。しかし、サイントラッカー（STS）のために、CSは魅力的で望ましいとなって、インセンティブの顕現で起因します。このレビューでは、PCAの手順を実行するために必要な機器、セットアップ、およびデータ処理の概要を説明します。加えて、我々は重要な実験的な検討事項を概説し、PCA訓練の代表的な結果を提供し、中毒およびその他の精神神経障害を調査中でPCA手順の推定上の有用性を議論します。

<table>
	<tbody>
		<tr>
			<td>Standard Modular Operant Test Chamber with Modified Top for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-008CT</td>
			<td>Top has access slot for drug delivery leashes or other harness systems; comes with ENV-008CTC (Cover Insert) for access slot</td>
		</tr>
		<tr>
			<td>Expanded PVC Sound Attenuating Cubicle</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-022V</td>
			<td></td>
		</tr>
		<tr>
			<td>PCI Operating Package for up to Sixteen Chambers</td>
			<td>Med Associates, Inc.</td>
			<td>MED-SYST-16</td>
			<td>Based on the number of operant chambers, MED-SYST-8 (PCI Operating Package for up to Eight Chambers) is also available</td>
		</tr>
		<tr>
			<td>SmartCtrl</td>
			<td>Med Associates, Inc.</td>
			<td>DIG-716P2</td>
			<td></td>
		</tr>
		<tr>
			<td>Universal Cable, 25&#8242; (7.6 m)</td>
			<td>Med Associates, Inc.</td>
			<td>SG-210CB</td>
			<td>Based on individual needs, SG-210CB-50 (Universal Cable, 50&#8242; [15.2 m]) is also available</td>
		</tr>
		<tr>
			<td>18&#8243; (45.7 cm) 3-Pin Mini-Molex</td>
			<td>Med Associates, Inc.</td>
			<td>SG-216A</td>
			<td>Based on individual needs, SG-216A-2 (2&#8242; [61.0 cm] 3-Pin Mini-Molex) is also available</td>
		</tr>
		<tr>
			<td>Power Cable, 25&#8242; (7.6 m)&#160;</td>
			<td>Med Associates, Inc.</td>
			<td>SG-210CP-25</td>
			<td></td>
		</tr>
		<tr>
			<td>Stainless Steel Grid Floor for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-005</td>
			<td>Based on preference, ENV-005A (Stainless Steel Grid Floor for Mouse) is also available&#160;</td>
		</tr>
		<tr>
			<td>Reusable Waste Pan</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-007-P3</td>
			<td></td>
		</tr>
		<tr>
			<td>Filler Panel Package for Standard Modular Test Chamber</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-008-FP</td>
			<td></td>
		</tr>
		<tr>
			<td>Modular Pellet Dispenser for Rat, 45mg</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-203M-45</td>
			<td></td>
		</tr>
		<tr>
			<td>Pellet Receptacle, Trough Type</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-200R2M</td>
			<td>Based on preference, ENV-200R1M (Pellet Receptable, Cup Type) is also available&#160;</td>
		</tr>
		<tr>
			<td>Retractable Lever</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-112CM</td>
			<td>Calibrated to 25 g; needs to be adjusted to 10 g before Pavlovian conditioned approach training</td>
		</tr>
		<tr>
			<td>Retractable Lever Cue Light</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-112CML</td>
			<td></td>
		</tr>
		<tr>
			<td>House Light for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-215M</td>
			<td></td>
		</tr>
		<tr>
			<td>100 mA Replacement Bulbs, Pack of 10</td>
			<td>Med Associates, Inc.</td>
			<td>SG-800R</td>
			<td>Red-colored; for use with ENV-215M (House Light for Rat)</td>
		</tr>
		<tr>
			<td>Pellets, 45 mg, Primate Purified Diet, Banana Flavor</td>
			<td>Bio-Serv</td>
			<td>F0059</td>
			<td>50,000/box&#160;</td>
		</tr>
	</tbody>
</table>

pavlovian conditioned approach training in rats

偶発的インセンティブの顕現の帰属、または魅力的に中性刺激の変換として知られるプロセスを通じてやりがいの性質そのものを取得することができる無条件、やりがいのある刺激と対になっているキューは、「行動をやる気にさせることが可能な刺激を求めていました。パブロフの条件付けのアプローチ（PCA） （米国; 例えば 、食品ペレット）無条件刺激の配信を予測し、（ 例えば 、レバーCS）条件刺激の応答に依存しないプレゼンテーションの後に発症し、インセンティブの顕現性トレーニングの間、3つのパターンを測定するために使用することができます。馴化応答（CRS）の開発することができます：サイン追跡行動（CS指向CR）、目標追跡行動（米国指向CR）、及び中間応答（両方CRを）サイントラッカー報酬に関連するインセンティブ顕現属性。 PCAポット作る手がかりと薬物探索の合図誘発性の復活だけでなく、他の嗜癖関連行動に対してより脆弱です、中毒の脆弱性を研究するためのentially貴重な手順。ここでは、ラットからPCAの動作を誘発するだけでなく、個々の実験でPCAの動作を分析し、解釈するために使用される材料および方法を記載します。

我々は、ラットを特定の実験室または実験の必要性に基づいてさらにトレーニングすることができるが、PCA訓練の5-7毎日のセッションは、STS、GTの、中間応答（IRS）などの表現型ラットに十分であることを見出しました。表現型は、以前のプロトコルに記載のように応答バイアス、待ち時間スコア、及び個々のセッションの確率差を平均することによって計算されるPC...

Watch this Scientific Journal Video about Pavlovian Conditioned Approach Training in Rats at JoVE.com

Pavlovian Conditioned Approach Training in Rats

Here, we present a protocol to elicit Pavlovian conditioned approach behavior in rats. This procedure can be used to measure individual differences in the tendency to approach and attribute incentive salience to reward-related cues and investigate addiction vulnerability.

ラットにおけるパブロフ馴化アプローチトレーニング

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the ...

pavlovian-conditioned-approach-training-in-rats

Research

JoVE Journal

Behavior

10.9K ビュー.  University of Michigan. Here, we present a protocol to elicit Pavlovian conditioned approach behavior in rats. This procedure can be used to measure individual differences in the tendency to approach and attribute incentive salience to reward-related cues and investigate addiction vulnerability. 

ビデオ: Pavlovian Conditioned Approach Training in Rats

Stereotaxic Microinjection of Viral Vectors Expressing Cre Recombinase to Study the Role of Target Genes in Cocaine Conditioned Place Preference

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes of interest allows for enhanced temporally- and regionally-specific control of gene deletion, compared to existing methods. While conditional deletion can also be achieved by mating mice that express Cre recombinase under the control of specific gene promoters with mice carrying a floxed gene, stereotaxic microinjection allows for targeting of discrete brain areas at experimenter-determined time points of interest. In the context of cocaine conditioned place preference, and other cocaine behavioral paradigms such as self-administration or psychomotor sensitization that can involve withdrawal, extinction and/or reinstatement phases, this technique is particularly useful in exploring the unique contribution of target genes to these distinct phases of behavioral models of cocaine-induced plasticity. Specifically, this technique allows for selective ablation of target genes during discrete phases of a behavior to test their contribution to the behavior across time. Ultimately, this understanding allows for more targeted therapeutics that are best able to address the most potent risk factors that present themselves during each phase of addictive behavior.

This article describes how to microinject viral vectors into mouse brain and then test in a conditioned place preference paradigm that includes an acquisition, extinction and reinstatement phase.

コカイン条件付け場所嗜好における標的遺伝子の役割を研究するためにCreリコンビナーゼを発現するウイルスベクターの定位マイクロインジェクション

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes ...

行動学

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

禁欲ラットで探しているヘロインに長期の食事制限の影響を研究するための手順

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

Training Synesthetic Letter-color Associations by Reading in Color

Synesthesia is a rare condition in which a stimulus from one modality automatically and consistently triggers unusual sensations in the same and/or other modalities. A relatively common and well-studied type is grapheme-color synesthesia, defined as the consistent experience of color when viewing, hearing and thinking about letters, words and numbers. We describe our method for investigating to what extent synesthetic associations between letters and colors can be learned by reading in color in nonsynesthetes. Reading in color is a special method for training associations in the sense that the associations are learned implicitly while the reader reads text as he or she normally would and it does not require explicit computer-directed training methods. In this protocol, participants are given specially prepared books to read in which four high-frequency letters are paired with four high-frequency colors. Participants receive unique sets of letter-color pairs based on their pre-existing preferences for colored letters. A modified Stroop task is administered before and after reading in order to test for learned letter-color associations and changes in brain activation. In addition to objective testing, a reading experience questionnaire is administered that is designed to probe for differences in subjective experience. A subset of questions may predict how well an individual learned the associations from reading in color. Importantly, we are not claiming that this method will cause each individual to develop grapheme-color synesthesia, only that it is possible for certain individuals to form letter-color associations by reading in color and these associations are similar in some aspects to those seen in developmental grapheme-color synesthetes. The method is quite flexible and can be used to investigate different aspects and outcomes of training synesthetic associations, including learning-induced changes in brain function and structure.

Reading in color is a new method for training letter-color associations that are typically found only in grapheme-color synesthetes. It involves an implicit form of training that has potential for long-term associative training methods&#160;because the training is a byproduct of reading and any text can be colored.

カラーで読み取ることにより、共感覚文字色の関連付けを訓練

Synesthesia is a rare condition in which a stimulus from one modality automatically and consistently triggers unusual sensations in the same and/or other ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

ラットにおけるパブロフ付きアルコール探索行動の状況誘発性のリニューアルを観察する手順

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.

Detailed instructions are provided on how to train rats to voluntarily dive underwater through a 5 m long Plexiglas maze. Because the brains of rats have been very well characterized, voluntarily diving rats may help elucidate the central pathways of the mammalian diving response.

自主ダイブ水中へのトレーニングラット：哺乳類ダイビング応答の調査

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a ...

Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats

Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that neural mechanisms for certain behavioral tasks and response behaviors are different in females and males. Using females in research studies can represent a challenge because of the variation of gonadal hormones during their estrous cycle. This protocol describes well-established procedures that are useful in investigating the role of estrogen in fear extinction memory consolidation in female rats. Phase of the estrous cycle and exogenous estrogen administration prior to extinction training can influence extinction recall 24 hr later. The vaginal swabbing technique for estrous phase identification described here aids the examination and manipulation of naturally cycling gonadal hormones. The use of this basic rodent model may further delineate the mechanisms by which estrogen can modulate fear extinction memory in females.

Gonadal hormones such as estrogen modulate memory formation in a number of experimental paradigms including fear extinction memory. This protocol describes a set of methods for investigating the influence of gonadal hormones specifically during extinction in naturally cycling females, including estrous cycle monitoring and exogenous estrogen administration.

当然の雌ラットをサイクリングで馴化恐怖の消滅を研究するためのプロトコル

Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

変更された穴会は - マウスとラットにおける行動、認知と社会的相互作用を測定する

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to drugs of abuse make lasting alterations in the brain function of vulnerable individuals, and these persistent alterations likely serve to maintain the maladaptive drug seeking and taking behaviors characteristic of addiction/dependence2. In rodents, reward experience and contextual associations are frequently measured using the conditioned place preference assay, or CPP, wherein preference for a previously drug-paired context is measured. Behavioral sensitization, on the other hand, is an increase in a drug-induced behavior that develops progressively over repeated exposures. Since sensitized behaviors can often be measured after several months of drug abstinence, depending on the dose and length of initial exposure, they are considered observable correlates of lasting drug-induced plasticity. Researchers have found these assays useful in determining the neurobiological substrates mediating aspects of addiction as well as assessing the potential of different interventions in disrupting these behaviors. This manuscript describes basic, effective protocols for mouse CPP and locomotor behavioral sensitization to cocaine.

This protocol is intended to enable researchers to conduct experiments designed to test these aspects of addiction using the conditioned place preference and locomotor behavioral sensitization assays.

コカイン誘発性行動感作の評価とマウスにおける条件付け場所嗜好

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

水剥奪、サッカリンフェージングまたは拡張アクセストレーニングなしでラットにおけるエタノールの補強性を評価するための方法

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits the evaluation of the conditioned rewarding effects of drugs related to environmental cues. Then, the extinguished CPP can be robustly reinstated by the non-contingent administration of a priming dose of the drug, and by exposure to stressful stimuli. Both methods will be explained here. When the animal reinitiates the behavioral response, a reinstatement of the conditioned reward is considered to have taken place.
The main advantages of this protocol are that it is non-invasive, inexpensive, and simple with good validity criteria. In addition, it allows the study of different environmental manipulations, such as stress or diet, which can modulate relapse into drug seeking behaviors. However, one limitation is that if the researcher aims to explore the motivation and primary reinforcing effects of the drug, it should be complemented with self-administration procedures, as they involve operant responses of animals.

This protocol describes the Conditioned Place Preference (CPP) as a model of relapse. This procedure permits the measurement of relapse in laboratory animals, considering the impact of drug-associated environmental cues as craving and relapse in abstaining addicts is currently the focus of drug-abuse treatment programs.

エアコンの場所の好みのパラダイムを使用してマウスの薬物探索の復権

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...