Lipopolysaccharide-induced depressive-like behavior is associated with α₁-adrenoceptor dependent downregulation of the membrane GluR1 subunit in the mouse medial prefrontal cortex and ventral tegmental area.
Bottom Line: Protein levels of the AMPA receptor GluR1 were significantly decreased at the plasma membrane in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA), while levels of the GluR2 were increased at the plasma membrane in the nucleus accumbens (NAc) at 24h after LPS.In opposition, administration of propranolol, a β-adrenoceptor antagonist, did not affect the LPS-induced downregulation of GluR1, the upregulation of GluR2, or the depressive-like behavior.These results suggest that LPS-activated α1-adrenoceptor-induced downregulation of membrane GluR1 in the mPFC and VTA is associated with inflammation-induced depressive-like behavior.
Affiliation: Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.Show MeSH
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Mentions: Before the investigation of LPS-induced neurobiological alterations in the mouse brain, we confirmed the effects of LPS on sickness behavior and depressive-like behavior to determine if the concentration of LPS was adequate. We measured the locomotor activity at 4 and 24h after LPS injection. A two-way ANOVA (time × treatment) on the mobility time in the open field test demonstrated a significant interaction (Figure 1A; F(1,20) = 72.8, p < 0.001). Bonferroni post-hoc tests revealed a significant difference between 4h post-LPS versus 4h post-saline (p < 0.001), but the decreased locomotor activity had recovered by 24h post-LPS (p = 0.429, 24h post-LPS vs. 24h post-saline). Furthermore, a significant decrease in body weight was observed at 24h post-LPS (Figure 1B; unpaired t-test, p = 0.0053). We next examined the mice at 24h post-saline or post-LPS for the assessment of LPS-induced depressive-like behavior in the TST and FST. The immobility time during the TST for the mice in the LPS group was significantly longer than for the mice in the control group (Figure 1C; unpaired t-test, p = 0.023). The immobility time during the FST for mice in the LPS group was also significantly longer than for the mice in the control group (Figure 1D, unpaired t-test, p = 0.013). In addition, LPS-injected mice showed a significantly lower preference for sucrose compared with the saline-injected mice at both 0–24h (Figure 1E; unpaired t-test, p = 0.004) and 24–48h post-LPS (Figure 1F; unpaired t-test, p = 0.047). These results indicate that the concentration of LPS used in the present study is an appropriate range for the assessment of depressive-like behavior.
Affiliation: Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.