The
“National Institutes of Health” genetically heterogeneous (NIH-HS) rat stock was
created in the 1980s through an eight-way cross of as much as possible separate
inbred rat strains (i.e. the MR/N, WN/N, WKY/N, M520/N, F344/N, ACI/N, BN/SsN
and BUF/N strains) which were readily available at that time. Hansen and Spuhler
[1] developed a more naturalistic, genetically heterogeneous rat stock with the
aim of optimizing the distribution of genotypic frequencies and recombination and
under the hypothesis that the NIH-HS stock could yield a broad-range distribution
of responses (broader than commonly used laboratory rat strains) to experimental
conditions, and thus serve as a base population for selection studies. Along the
last decade, in a series of studies we have phenotypically characterized the NIH-HS
rat stock (a colony exists at our laboratory since 2004) for their anxiety/fearfulness
profiles (using a battery of both unconditioned and conditioned tests/tasks),
as well as regarding their stress-induced hormonal responses, coping style under
inescapable stress and spatial learning ability. We have also compared the phenotypic
profiles of NIH-HS rats with those of the low anxious RHA-I and the high anxious
RLA-I rat strains. The NIH-HS rat stock is, as a population, a rather anxious type
of rat, with predominantly reactive/passive coping style in unlearned and learned
anxiety/fear tests, and elevated stress hormone responses (as well as enhanced “depressive”
symptoms in the forced swimming test). Genetic studies currently under way have
thus far revealed that the genetically heterogeneous NIH-HS rat stock constitutes
a unique tool for fine mapping of QTL (for multiple behavioural and biological complex
traits) to megabase resolution levels, thus enabling candidate gene identification.
We give some examples of this in the present paper, while also highlighting that
microarray gene expression studies reveal that HPA-axis- and prolactin-related genes
(among others) in the amygdala appear to be related with (or associated to) the
coping style and anxiety/fearfulness responses of NIH-HS rats.