GABAergic elimination in the ventral hippocampus induces anhedonia.

Abstract

It has been suggested that the development of depression involves a reduction in GABAergic neurons. However, the underlying mechanism remains to be fully elucidated. In this study, we examined whether GABAergic elimination in the ventral hippocampus induces anhedonia, a core symptom of depression. Male ddY mice were bilaterally injected with saporin-conjugated anti-GABA transporter-1 antibodies (GAT1sp) in the ventral hippocampus, and then were subjected to a sucrose preference test 10 days after GAT1sp injection. Another cohort of mice received a combined chronic mild stress with ACTH treatment (ACMS) for 4 weeks, and was subjected to a sucrose preference test. Immunofluorescence was performed to detect the parvalbumin, GFAP, and pERK. In both the GAT1sp and the ACMS groups, compared to the PBS and non-stress groups respectively, there were significant decreases in sucrose preference as well as the parvalbumin-positive cell densities in the hippocampus. GFAP-positive cell densities were decreased in the ventral hippocampus of the ACMS group, but not the GAT1sp group. pERK-positive cell densities were increased in the nucleus accumbens of both the GAT1sp and ACMS groups. Together, similar to chronic stress, GABAergic elimination in the ventral hippocampus induces anhedonia accompanied by activation of ERK signal transduction in the nucleus accumbens.