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

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 α 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. 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-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 Gα_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, Gα_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 Gα_z knock-outs. Conclusions: 5-HT_1A receptors couple to G_z. In a strictly background strain-dependent manner, Gα_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 Gα_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.