Moderata esposizione prenatale di alcool e quantificazione di comportamento sociale in ratti adulti
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
Si stima che circa 1-5% dei bambini sono diagnosticati con Fetal Alcohol Spectrum Disorders (FASDs) 2, che comprendono la sindrome alcolica fetale (FAS), parziale FAS (PFA), e alcolcorrelati dello sviluppo neurologico Disturbi (ARNDs) 3. I deficit nel comportamento sociale e cognizione sono tra gli esiti avversi più comuni osservati nei bambini con FASDs 4-7. Conseguenze negative non sono limitati a forte esposizione prenatale (PAE), come moderato PAE che non porta al deficit morfologici, comportamentali e cognitivi cospicua caratteristica del FAS può causare relativamente sottili, ma comunque persistente, deficit negli esseri umani con FASDs 8-10 e gli animali non umani esposti all'etanolo durante lo sviluppo del cervello 11. L'importanza di comprendere le conseguenze neurobiologiche comportamentali e corrispondenti di moderata PAE è sottolineata da stime attuali indicano che la grande maggioranza dei casi FASD rientrano fra le meno sgamma Evere dello spettro 12.
Diversi laboratori indipendenti hanno segnalato alterazioni roditore comportamento sociale legati a etanolo esposizione durante lo sviluppo del cervello, tra cui una diminuzione di indagine e di interazione 1,13-15, alterata gioco 14,16,17, aumento interazioni aggressive 17,18, alterazioni nella risposta a stimoli sociali 19-21, e deficit in preferenze alimentari socialmente acquisite e la memoria di riconoscimento sociale 22. Deficit comportamento sociale sono stati osservati a seguito dell'esposizione ad pesanti (concentrazioni di etanolo nel sangue (BECS) ~ 300 mg / dl) 22,23 o livelli più moderati di etanolo (BEC ~ 80mg / dl) 1, e attraverso una vasta gamma di parametri per altro significativo fattori, tra cui i tempi di esposizione, durata dell'esposizione, e l'età al momento della valutazione del comportamento.
Precedenti ricerche hanno dimostrato che le alterazioni in aspetti specifici di int socialeeraction in età adulta discriminare ratti esposti a livelli moderati di alcol da animali di controllo esposti a saccarina 1,18. In particolare, moderata PAE ha sempre stato associato con aumenti robusti di wrestling, che suggerisce un aumento del comportamento aggressivo, e più bassi livelli di indagine sociale (ad esempio, fiutando del partner) in età adulta. Perché alterazioni nel comportamento sociale sono conseguenze affidabili PAE, la quantificazione del comportamento sociale in seguito PAE può tenere importanza per progredire verso una più completa comprensione delle basi neurali di alterazioni PAE-correlate nel comportamento sociale e lo sviluppo di approcci interventistici. L'obiettivo di questo documento e il video associato è di fornire istruzioni sul protocollo PAE moderato e metodi per la quantificazione del comportamento sociale in figli adulti che hanno affidabile distinto prenatale alcol esposti da prole non esposti rat.
Protocol
Representative Results
Discussion
Il paradigma esposizione prenatale qui descritto comporta il consumo volontario di etanolo (5% v / v) di dighe ratto durante la gravidanza. Ci sono un certo numero di protocolli per esporre gli animali non umani a etanolo durante lo sviluppo cerebrale rappresentato in letteratura, che differiscono rispetto alla temporizzazione, dose, la durata e la via di somministrazione etanolo nonché specie in esame. Anche se uno studio approfondito dei vantaggi dei vari protocolli di esposizione non è fornito qui, numerosi vantagg…
Divulgazioni
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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