Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice

Abstract

Routine laboratory procedures, such as handling or transporting animals or carrying out injections on animals, are stressful for animals but are necessary in many pre-clinical studies. Here, the authors show that multiple injections of the non-toxic vehicle cyclodextrin moderately increased plasma corticosterone concentrations in female BALB/c mice. Additionally, male BALB/c mice that had received a single intraperitoneal injection of harmless saline had an increased glucocorticoid response to a second saline injection. The authors found that female mice that had been exposed to an acute psychological stress session had a decreased glucocorticoid response to a second homotypic stressor. In contrast, multiple psychological stress sessions led to increased glucocorticoid release in female mice. Acute injection(s) of saline in male mice and of cyclodextrin in female mice led to transient lymphocytopenia. Further analysis showed that repeated stress-induced lymphocytopenia is glucocorticoid-dependent. The authors conclude that laboratory stress can affect physiological parameters in mice, potentially altering study results.

Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis

“…However, mice that received a saline injection had a modest increase in activated microglia with activated morphologies that we observed in uninjected mice (Fig. 4E) indicating that the stress of IP injections alone can cause an immune response as has been observed by others [48,49]. Overall, these results suggest that sustained microglia activation and inflammation in young adult mice (2 months old) significantly reduces neurogenesis in the V-SVZ.…”

Novel intrathecal and subcutaneous catheter delivery systems in the mouse

“…Though multiple injection protocols are commonly used to deliver drugs to peripheral regions, they cannot achieve consistent drug delivery over an extended period of time (Fara and Urquhart 1984; Perkins et al 2004). Further, repeated injections expose the animal to excessive handling and injury, often confounding the results of physiological and behavioral experiments (Wright and Lincoln 1985; Dilsaver and Majchrzak 1990; Lafarga et al 1998; Vinkers et al 2009; Drude et al 2011). …”

Pre- and Neonatal Exposure to Lipopolysaccharide or the Enteric Metabolite, Propionic Acid, Alters Development and Behavior in Adolescent Rats in a Sexually Dimorphic Manner

“…Prenatally stressed rats have been shown to be hyperactive in a novel open-field, as well as displaying anxiety-like behavior [54], [55]. Repeated injections can alter baseline levels of plasma corticosterone [56], [57] and prenatal stress can compromise the placental barrier, exposing developing animals to corticosterone [58]. This may have led to greater activity in a potentially stressful situation, in this case, a novel open-field.…”