Comprehensive behavioral characterization of Gpm6b null mutants as a mouse model of depression
Year: 2013
Type: dissertation
Abstract: In this thesis male Gpm6b null mutants on a C57BL/6J background were characterized in
various behavioral test settings. Gpm6b null
mutants, as yet an entirely uncharacterized mouse strain, are lacking the
glycoprotein M6B that inhibits the serotonin transporter surface expression.
Knockout of the Gpm6b gene may lead to a depressive-like phenotype in these
mice due to a surface overexpression of serotonin
transporters and hence a more efficient clearing of serotonin from the
synaptic cleft. The
performed tests could show distinct changes in the behavior
of Gpm6b null mutants making this strain a promising mouse model of
depression. Gpm6b null mutants demonstrated an increased velocity in the
elevated plus maze test interpreted as mild hyperactivity similar to
agitation seen in human patients suffering from depression. Gpm6b null
mutants revealed an increase in immobility time in the forced swim test - a
test that is typically used to assess depressive-like behavior
in rodents. Hints for reduced contextual fear extinction were observable in
these mice suggesting an impaired extinction of aversive memories.
Additionally, an impaired PPI would be in line with the involvement of the serotonergic system. The i.p.-injection
of the 5-HT2A/2C receptor agonist (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane
hydrochloride (DOI) at a dose of 0.5 mg/kg demonstrated the divergent effects
of the drug depending on the genotype. Whereas the administration of DOI
caused a reduction of locomotor activity in wildtype mice after a short delay, Gpm6b null mutants
were less susceptible, consistent with less serotonin in the synaptic cleft.
Furthermore, the injection of the pro-inflammatory substance lipopolysaccharide (250 μg/kg on two consecutive days, i.p) to wildtype mice
and Gpm6b null mutants revealed that Gpm6b null mutants did not exhibit the
temporarily reduced locomotor activity found in wildtype mice.
To conclude, behavioral
tests revealed a mild depressive-like phenotype in Gpm6b null mutants. Pharmacological
challenges (DOI, LPS) support an involvement of the serotonergic
system in the observed phenotype.
Author: Caroline Ritter
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2183882105