Open AccessSerotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks
Author(s) -
Muller J. M.,
Morelli E.,
Ansorge M.,
Gingrich J. A.
Publication year - 2011
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2010.00652.x
Subject(s) - serotonin transporter , psychology , fear conditioning , heterozygote advantage , neuroscience , anxiety , open field , 5 httlpr , serotonin plasma membrane transport proteins , serotonin , allele , developmental psychology , genotype , gene , biology , genetics , amygdala , psychiatry , receptor
Modulation of serotonin transporter (5‐HTT) function causes changes in affective behavior, both in humans and rodents. Stressful life events likewise affect emotional behavior. In humans, a low‐expressing genetic 5‐htt variant, the s allele of the 5‐htt linked promoter region, has been associated with increased risk for depression only where there was a history of stressful life events. To investigate this gene by environment interaction in mice, we compared the effects of inescapable shocks on the behavior of wild‐type ( 5‐htt +/+), heterozygote ( 5‐htt +/−) and serotonin transporter deficient ( 5‐htt −/−) mice. Inescapable shocks induce behavioral changes including a shock escape deficit, in a subsequent test when escape is possible. Confirming a gene by environment interaction, we found that stress increases escape latencies in a gene‐dose dependent manner ( 5‐htt −/−> 5‐htt +/−> 5‐htt +/+), where as there were no differences among the genotypes in the unstressed condition. The vulnerability to increased escape latency could not be accounted for by enhanced fear learning, as 5‐htt −/− mice did not show heightened fear conditioning. The interaction of 5‐htt genotype and stress appeared to produce a selective behavioral vulnerability, because no interaction of 5‐htt genotype and stress was observed in other measures of anxiety and depression‐linked behavior, including the open field, novelty suppressed feeding, and forced swim tests. We replicated prior findings that the 5‐htt −/− displays heightened anxiety and depression‐like behavior at baseline (unstressed condition). In conclusion, our data offer the possibility for future investigation of the neural basis underlying 5‐htt genotype‐by‐stress interaction shown here.