Vglut2 haploinsufficiency enhances behavioral sensitivity to MK-801 and amphetamine in mice

Recently developed mouse models have implicated the vesicular glutamate transporter 2 (VGLUT2) in psychostimulant-induced hyperactivity, a behavioral assay that is often applied to evaluate mouse behavior related to positive schizophrenia (SCZ) symptomatology. In present research, we wanted to evaluate further the role of subtle VGLUT2 impairment as a factor underlying SCZ symptomatology. To this end, we evaluated Vglut2 haploinsufficient (Vglut2⁺/⁻) mice and their wildtype littermates in a test battery assessing behaviors related to positive, negative and cognitive SCZ symptom domains. We found in Vglut2⁺/⁻ mice an increased locomotor response to amphetamine and an increased sensitivity to the startle-disrupting effects of MK-801, but no impairment in sensorimotor gating. Further on, minor alterations in tests assessing cognitive and negative symptom-related behavior were observed. Possible neurobiological mechanisms of these observations are discussed.