Moderat Prænatal Alkohol Eksponering og kvantificering af social adfærd hos voksne rotter
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
Det anslås, 1-5% af alle børn er diagnosticeret med Føtalt Alkohol Spectrum Disorders (FASDs) 2, som omfatter Føtalt Alkohol Syndrom (FAS), delvis FAS (pFAS), og alkoholrelaterede forstyrrelser i nervesystemets udvikling (ARNDs) 3. Underskud i social adfærd og kognition er blandt de mest almindelige bivirkninger resultater observeret hos børn med FASDs 4-7. Negative konsekvenser er ikke begrænset til tunge prænatal alkohol eksponering (PAE), som moderat PAE, der ikke fører til iøjnefaldende morfologiske, adfærdsmæssige og kognitive mangler karakteristiske for FAS kan forårsage forholdsvis subtile, men ikke desto mindre vedholdende, underskud i mennesker med FASDs 8-10 og ikke-humane dyr udsat for ethanol under hjernens udvikling 11. Det er vigtigt at forstå de adfærdsmæssige og tilsvarende neurobiologiske konsekvenser af moderat PAE understreges af de nuværende skøn tyder på, at det store flertal af FASD sager falder inden for de mindre sEvere område af spektret 12.
Flere uafhængige laboratorier har rapporteret ændringer i gnaver social adfærd i relation til ethanol eksponering under hjernens udvikling, herunder nedsat undersøgelse og interaktion 1,13-15, ændret play 14,16,17, øget aggressive interaktioner 17,18, ændringer i modtagelighed for sociale stimuli 19-21, og underskud i socialt erhvervede fødevarer præferencer og social anerkendelse hukommelse 22. Social adfærd underskud er blevet observeret efter eksponering for tunge (blod ethanolkoncentrationer (BECS) ~ 300 mg / dl) 22,23 eller mere moderate niveauer af ethanol (BEC ~ 80 mg / dl) 1, og på tværs af en bred vifte af parametre for andre væsentlige faktorer, herunder eksponering timing, varighed af eksponering, og alder på det tidspunkt, adfærdsmæssige måling.
Tidligere forskning har vist, at ændringer i specifikke aspekter af social interaction i voksenalderen diskriminere rotter udsat for moderate niveauer af alkohol fra kontroldyr udsat for saccharin 1,18. Især har moderat PAE konsekvent været forbundet med robuste stigninger i brydning, hvilket tyder stigninger i aggressiv adfærd, og lavere niveauer af social undersøgelse (f.eks snifning af partner) i voksenalderen. Fordi ændringer i social adfærd er pålidelige konsekvenser af PAE kan kvantificering af social adfærd efter PAE holde betydning for fremskridt i retning af en mere fuldstændig forståelse af de neurale grundlag for PAE-relaterede ændringer i social adfærd og udvikling af interventionelle tilgange. Målet med dette papir og den tilhørende video er at give instruktion på moderate PAE protokol og metoder til kvantificering af social adfærd hos voksne afkom der har pålideligt skelnes prænatal alkohol-eksponerede fra ikke-eksponerede rotte afkom.
Protocol
Representative Results
Discussion
Den prænatal alkohol eksponering paradigme beskrevet her involverer frivillig indtagelse af ethanol (5% v / v) af rotte dæmninger under graviditet. Der er en række af protokoller for at udsætte ikke-menneskelige dyr til ethanol under hjernens udvikling repræsenteret i litteraturen, som er forskellige med hensyn til timing, dosis, varighed og rute for ethanol administration samt de arter, der undersøges. Selv om en grundig behandling af fordelene ved forskellige protokoller eksponering ikke leveres her, flere forde…
Disclosures
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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