Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks.
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.
Department of Developmental Neuroscience, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
J M
JM
Muller
E
E
Morelli
M
M
Ansorge
J A
JA
Gingrich
D000483:Alleles; D000818:Animals; D003863:Depression / Q000523:psychology; D004597:Electroshock; D004777:Environment; D004924:Escape Reaction / Q000502:physiology*; D005239:Fear / Q000502:physiology / Q000523:psychology; D005247:Feeding Behavior; D018628:Gene Dosage; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology; D013550:Swimming / Q000523:psychology
D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse