Effect of Lithium Carbonate on the Enhancement of Serotonin 2A Receptor Elicited by Dexamethasone

Abstract

The purpose of this study was to investigate whether chronic dexamethasone (Dex) administration induces serotonin (5-HT) 2A receptor supersensitivity and if chronic lithium carbonate (Li) administration contributes to the normalization of 5-HT2A receptor supersensitivity induced by Dex in rat brain. We investigated the effects of a 14-day administration of Dex and/or Li on changes in body weight (BW), on plasma corticosterone levels, on plasma lithium levels, on 5-HT2A receptor binding sites, and on (±)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI)-induced wet dog shake (WDS), which is mediated by 5-HT2A receptor in rats. Dex significantly reduced the BW of rats. Li did not have any effect on BW gain and did not prevent the BW loss induced by Dex. The plasma corticosterone levels of rats treated with Dex were too low to be detected. Li did not have any effect on corticosterone levels and did not prevent the decrease in the corticosterone levels induced by Dex. Six hours after the last treatment, the plasma lithium levels of rats treated with Li were significantly higher than those of rats treated with Dex/Li. Chronic Dex administration resulted in a significant increase in the density (B_max) of the 5-HT2A receptor without a significant change in the affinity (K_d). The increase in the B_max induced by Dex was not prevented by chronic combined treatment with Dex and Li. Chronic Dex administration potentiated the WDS, and this increase was prevented by chronic combined treatment with Dex and Li. Chronic Li administration did not have any effect on WDS. These results indicate that chronic Li administration may improve the supersensitivity of the 5-HT2A receptor elicited by chronic Dex administration without decreasing the density of the 5-HT2A receptor, and the effect of Li was also independent of hypothalamo-pituitary-adrenal axis function.

Pivotal mental states

“…We place special focus on the serotonin system and its 2A receptor (5-HT2AR) subtype in particular, which has been shown to be particularly implicated in biology x environment interactions (Chang et al, 2017; Dressler et al, 2016; Fiocco et al, 2007; Jiang et al, 2016; Jokela et al, 2007; Lebe et al, 2013; Mellman et al, 2009; Parade et al, 2017; Salo et al, 2011). Various acute stressors appear to be reliable and robust inducers of serotonin release (Adell et al, 1997; Amat et al, 1998, 2005; Bastani et al, 2017; Beitia et al, 2005; Bland et al, 2003; Cohen et al, 2015; Ferres-Coy et al, 2013; Fuenmayor and Garcia, 1984; Fujino et al, 2002; Gardner et al, 2005; Hale et al, 2011; Higuchi et al, 2019; Ishida et al, 1997; Ishiwata and Greenwood, 2018; Johnson et al, 2005; Keeney et al, 2006; Kelly et al, 2011; Li et al, 2015; Myers and Beleslin, 1971; Nakajima et al, 2009; Neugebauer, 2020; Paul et al, 2011; Rex et al, 2005; Yoshioka et al, 1995) and different types of stressor, such as sleep deprivation (Elmenhorst et al, 2012; Maple et al, 2015; Zhao et al, 2019), hypoxia (Anju et al, 2011), chronic tryptophan depletion (Cahir et al, 2007), inflammation (Zhang et al, 2001), tonic pain (Kupers et al, 2009), repeated forced swim (Takao et al, 1995), repeated shock (Dwivedi et al, 2005), administration of stress hormones (Jitsuiki et al, 2000; Kuroda et al, 1992, 1994), amygdala stimulation (…”