Mice deficient in the alpha subunit of G(z) show changes in pre-pulse inhibition, anxiety and responses to 5-HT(1A) receptor stimulation, which are strongly dependent on the genetic background.
BACKGROUND
G(z), a member of the G(i) G protein family, is involved in the coupling of dopaminergic and serotonergic receptors. In the present study, we investigated behaviour of mice deficient in the alpha subunit of G(z) and focused on pre-pulse inhibition (PPI) and anxiety-like responses and the role of serotonin-1A (5-HT(1A)) receptors.


METHODS
We compared male and female wild-type and knock-out mice on either a C57Bl/6 or Balb/c background. We used automated startle boxes to assess startle and PPI and elevated plus maze to assess anxiety-like behaviours.


RESULTS
Balb/c mice showed higher baseline PPI than C57Bl/6 mice, and there was no difference between the genotypes. The 5-HT(1A) receptor agonist, 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), had no effect on PPI in C57Bl/6 mice but markedly increased PPI in Balb/c mice, with the effect being attenuated in Galpha(z) knock-outs. On the elevated plus maze, there was little effect of the knock-out or 8-OH-DPAT in C57Bl/6 mice, whereas in Balb/c mice, Galpha(z) knock-outs showed a phenotype of high levels of anxiety-like behaviour. 8-OH-DPAT was anxiogenic in Balb/c mice, but this effect was attenuated in Galpha(z) knock-outs.


CONCLUSIONS
5-HT(1A) receptors couple to G(z). In a strictly background strain-dependent manner, Galpha(z) knock-out mice display high levels of anxiety-like behaviour and are less sensitive to the action of 8-OH-DPAT. Balb/c mice show much more clear effects of the Galpha(z) knock-out than C57Bl/6 mice, which are often considered the standard background strain for genetic modifications. Therefore, our results suggest caution when studying the behavioural effects of genetic modifications only in C57Bl/6 mice.
van den Buuse
Maarten
M
Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, Parkville, Victoria 3052, Australia. mvandenbuuse@mhri.edu.au
Martin
Sally
S
Holgate
Joan
J
Matthaei
Klaus
K
Hendry
Ian
I
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle / Q000235:genetics*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012737:Sex Factors; D015398:Signal Transduction; D013045:Species Specificity
D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin