Behavioural phenotyping of sodium-myo-inositol cotransporter heterozygous knockout mice with reduced brain inositol.
Inositol plays a key role in dopamine, serotonin, noradrenaline and acetylcholine neurotransmission, and inositol treatment is reported to have beneficial effects in depression and anxiety. Therefore, a reduction in brain intracellular inositol levels could be a cause of some psychiatric disorders, such as depression or anxiety. To determine the behavioural consequences of inositol depletion, we studied the behaviour of sodium-dependent myo-inositol cotransporter-1 heterozygous knockout mice. In heterozygous mice, free inositol levels were reduced by 15% in the frontal cortex and by 25% in the hippocampus, but they did not differ from their wild-type littermates in cholinergic-mediated lithium-pilocarpine seizures, in the apomorphine-induced stereotypic climbing model of dopaminergic system function, in the Porsolt forced-swimming test model of depression, in amphetamine-induced hyperactivity, or in the elevated plus-maze model of anxiety. Reduction of brain inositol by more than 25% may be required to elicit neurobehavioural effects.
Shaldubina
A
A
Stanley Research Centre, Faculty of Health Sciences, Ben Gurion University of the Negev, Israel.
Buccafusca
R
R
Johanson
R A
RA
Agam
G
G
Belmaker
R H
RH
Berry
G T
GT
Bersudsky
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism*; D007294:Inositol / Q000172:deficiency / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010641:Phenotype; D027981:Symporters / Q000235:genetics / Q000502:physiology*
C508355:SLC5A3 protein, mouse; D027981:Symporters; D007294:Inositol