Vglut2 haploinsufficiency enhances behavioral sensitivity to MK-801 and amphetamine in mice |
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Authors: | Naert Arne Callaerts-Vegh Zsuzsanna Moechars Diederik Meert Theo D'Hooge Rudi |
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Affiliation: | a Laboratory of Biological Psychology, Department of Psychology, University of Leuven, Tiensestraat 102, B-3000 Leuven, Belgiumb Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium |
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Abstract: | 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. |
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Keywords: | %PPI, percentage prepulse inhibition %SA, percentage spontaneous alternation ANOVA, analysis of variance DA, dopamine GABA, γ-aminobutyric acid NMDA, N-methyl-D-aspartate PC, personal computer PP, prepulse PPI, prepulse inhibition PP SPL, prepulse sound pressure level RM-ANOVA, repeated measures analysis of variance SCZ, schizophrenia SEM, standard error of the mean SP, startle pulse SPL, sound pressure level VGLUT, vesicular glutamate transporter Vglut2/VGLUT2, vesicular glutamate transporter 2 (gene/protein or mRNA) Vglut2+/&minus , Vglut2 heterozygote Vglut2+/+, Vglut2 wildtype VTA, ventral tegmental area |
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