Mice deficient in the alpha subunit of Gz show changes in pre-pulse inhibition, anxiety and responses to 5-HT1A receptor stimulation, which are strongly dependent on the genetic background

Rationale 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 prepulse inhibition ( PPI) and anxiety-like responses and the role of serotonin-1A (5-HT1A) receptors. Materials and 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-HT1A 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 G alpha(z) knock-outs. On the elevated plus maze, there was little effect of the knock-out or 8-OH-DPAT C57Bl/6 mice, whereas in Balb/c mice, Gaz 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 Gaz knock-outs. Conclusions 5-HT1A receptors couple to G(z). In a strictly background strain-dependent manner, G alpha(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 G alpha(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.