Matige Prenatale blootstelling aan alcohol en kwantificering van sociaal gedrag bij volwassen ratten
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
Naar schatting 1-5% van de kinderen zijn gediagnosticeerd met Foetaal Alcohol Spectrum Stoornissen (FASDs) 2, die Foetaal Alcohol Syndroom (FAS), gedeeltelijke FAS (PFAS), en alcohol gerelateerde Neurodevelopmental Disorders (ARNDs) 3 bevatten. Tekorten in sociaal gedrag en cognitie behoren tot de meest voorkomende negatieve resultaten waargenomen bij kinderen met FASDs 4-7. Negatieve gevolgen zijn niet beperkt tot zware prenatale blootstelling aan alcohol (PAE), matige PAE die niet leidt tot de opvallende morfologische, gedrags- en cognitieve tekorten kenmerkend FAS kan relatief subtiel, maar toch hardnekkige veroorzaken tekorten bij mensen met FASDs 8-10 en niet-menselijke dieren blootgesteld aan alcohol tijdens hersenontwikkeling 11. Het belang van het begrijpen van de gedrags- en overeenkomstige neurobiologische gevolgen van matige PAE wordt onderstreept door de huidige schattingen geven dat het merendeel van de FASD zaken binnen minder s vallenEvere bereik van het spectrum 12.
Verschillende onafhankelijke laboratoria hebben gemeld veranderingen in knaagdieren sociaal gedrag in verband met blootstelling ethanol tijdens de hersenontwikkeling, waaronder verminderde onderzoek en interactie 1,13-15, veranderd play 14,16,17, verhoogde agressieve interacties 17,18, wijzigingen in de gevoeligheid voor sociale stimuli 19-21, en tekorten in sociaal verworven voedsel voorkeuren en geheugen maatschappelijke erkenning 22. Sociaal gedrag tekorten zijn waargenomen na blootstelling aan zware (bloed ethanol concentraties (Becs) ~ 300 mg / dl) 22,23 of meer gematigde niveaus van ethanol (Becs ~ 80 mg / dl) 1, en in een breed scala van parameters voor andere belangrijke factoren, waaronder blootstelling timing, blootstellingsduur en de leeftijd bij gedrags- meting.
Eerder onderzoek heeft aangetoond dat veranderingen in specifieke aspecten van sociale interaction op volwassen leeftijd discrimineren ratten blootgesteld aan gematigde niveaus van alcohol uit controle dieren blootgesteld aan sacharine 1,18. Vooral gematigd PAE consistent geassocieerd met robuuste toename worstelen, waarbij verhogingen van agressief gedrag, en lagere sociaal onderzoek (bijv snuiven van de partner) in volwassenheid suggereert. Omdat veranderingen in sociaal gedrag zijn betrouwbaar gevolgen van PAE, kan de kwantificering van sociaal gedrag volgende PAE belang houden voor vooruitgang in de richting van een meer volledig begrip van de neurale basis van PAE-gerelateerde veranderingen in sociaal gedrag en de ontwikkeling van interventionele benaderingen. Het doel van dit document en de bijbehorende video is het geven van instructie op de gematigde PAE-protocol en de methoden voor het kwantificeren van sociaal gedrag bij volwassen nakomelingen die moeten betrouwbaar onderscheiden prenatale alcohol blootstelling van niet-blootgestelde nakomelingen rat.
Protocol
Representative Results
Discussion
De prenatale blootstelling alcohol paradigma beschreven omvat vrijwillige gebruik van ethanol (5% v / v) door dammen rat tijdens de zwangerschap. Er zijn een aantal protocollen voor het blootstellen van niet-menselijke dieren ethanol tijdens hersenontwikkeling voorgesteld in de literatuur, die verschillen wat betreft de timing, dosering, duur en route van toediening ethanol alsmede de soort onderzochte. Hoewel een grondige behandeling van de voordelen van verschillende blootstelling protocollen hier niet wordt verstrekt…
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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