Objective: To evaluate cognitive and depressive behavior in aged mice with heterozygous deletions of vesicular monoamine transporter (VMAT2) or of Dopamine transporter (DAT).

Background: VMAT2 and DAT have long been known to compartmentalize and accumulate Dopamine (DA), regulating levels of DA in neuronal compartments. Furthermore, possible roles for VMAT2 and DAT in other monoamine systems (norepinephrine, serotonin) were shown previously, indicating animals with genetically modified levels of VMAT2 and DAT may be potent models to study non-motor symptoms.

Methods: Aged (12 months) heterozygous VMAT2 KO mice (VMAT2+/-) and heterozygous DAT KO mice (DAT+/-) combined with the wild-type mice were included in our experiment. 30 mg/kg rotenone once a day for 56 d were given by gavage to induce Parkinson’s disease models. We then evaluate behaviors in all of these three models: Morris water maze was used to assess cognition, tail suspension test and sucrose preference test were used to estimate depression.

Results: VMAT2 (+/-) mice display depression–like behavior and rotenone aggravate this phenomenon, while this was not obvious in DAT+/- mice even treated with rotenone. When referring to cognitive impairment, it was observed in DAT+/- mice and deteriorated after rotenone-treated DAT+/- mice. However, there was no evidence of cognitive impairment in VMAT2 (+/-) and rotenone-treated VMAT2 (+/-) mice.

Conclusions: Heterozygous deletions of VMAT2 or of DAT display depressive or cognitive behavior. The two genetically modified animals may be good candidates to study depression and cognitive impairment in Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-and-depressive-behavior-changes-in-aged-mice-with-heterozygous-deletions-of-vmat2-or-of-dat/