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Semi Natural Environment and Oxytocin Knock Out Mice

FEMALE OXCYTOCIN GENE KNOCKOUT MICE IN A SEMI-NATURAL ENVIRONMENT, DISPLAY INCREASED AGGRESSIVE BEHAVIOR.

Ragnauth, A., Devidze, N., Moy, V., Muglia, L.J., Pfaff, D.W.

Introduction

Laboratory of Neurobiology & Behavior, The Rockefeller University, New York, NY1, Department of Molecular Biology & Pharmacology, Washington University School of Medicine2, St. Louis, MS.

Oxytocin (OT) in the brain is classically viewed as primarily involved in the milk letdown reflex and in the stimulation of uterine smooth muscles during parturition. Its role in aggression is less clear with contradictory findings, both facilitation of aggression (Ferris et al, 1990; Giovenardi et al, 1998) and reduction in aggression (De Vries et al, 1997) in mice.

The interaction between genotype and environment is of considerable importance in the study of genetically altered mice. Studies under standard laboratory conditions makes it difficult to accurately determine environmental influences on genetically determined forces (Cabib et al, 2000; Potts et al, 1991). Semi-natural conditions have been used to create complex competitive and stressful conditions designed to mimic nature (Huck et al, 1988), and so unveil behaviors previously indiscernible in the standard lab environment (Gilbert et al, 1980). This is especially relevant when one considers that genes evolved to function optimally in large complex interactive environments.

Food and water challenges have previously been used to create a situation closer to that in the wild since food restriction is an ecologically relevant and common event in the wild (Kanarek & Marks-Kaufman 1988). The introduction of a female into a males' environment, or vice versa, is a well-established method for the study of sexual behavior. Similarly, the resident-intruder paradigm has frequently been used to study the effect of the introduction of a stranger into the midst of an extant social grouping (see review, Miczek et al, 2001).

Transgenic technology provides a precise tool for behavioral research by being able to disrupt a single, targeted, gene. With the creation of specific gene-knockouts, transgenic mice - wild type, heterozygous and knockout - can be used in experiments to effectively determine the actual role of a gene and its product in behavior. Transgenic technology has produced oxytocin-peptide knockout mice (Nishimori et al., 1996; Gross et al., 1998). However, oxytocin-knockout (OTKO) mice have failed to show many of the expected behavioral deficits. For example, female OTKO did not display any changes in their maternal behavior towards their pups (Nishimori et al., 1996; Young et al, 1997), and OTKO mice have shown reduced aggression compared to their WT counterparts (DeVries et al, 1997).

Using OTKO and WT mice, we propose to examine the behavioral consequences of residence in a large semi-natural environment, specifically, by following a food restriction challenge and by providing the opportunity for sexual interaction through the introduction of males into a females only environment.