Zoopharmacognosy in Diseased Laboratory Mice: Conflicting Evidence

Abstract

Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY), an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice

“…Such a non-invasive administration route was chosen to avoid confounding effects of repeated pain- and restraint-induced stress on behavioral performance [ 7 , 74 , 98 ]. Moreover, due to its metallic taste, CY was laced with sucrose to increase palatability and thus achieve the therapeutic dose range previously shown to attenuate systemic autoimmunity and normalize functional deficits in lupus-prone mice [ 57 ]. In order to assess general CY toxicity, we similarly treated WT mice to control for multisystem effects of CY and its metabolites that are not related to the immune system.…”

Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer’s Disease-Associated Markers in 3xTg-AD Mice

“…Such a non-invasive administration route was chosen to avoid confounding effects of repeated pain-and restraint-induced stress on behavioral performance [6,70,93]. Moreover, due to its metallic taste, CY was laced with sucrose to increase palatability and thus achieve the therapeutic dose range previously shown to attenuate systemic autoimmunity and normalize functional de cits in lupus-prone mice [54]. In order to assess general CY toxicity, we similarly treated WT mice to control for multisystem effects of CY and its metabolites that are not related to the immune system.…”

Effects of sustained i.c.v. infusion of lupus CSF and autoantibodies on behavioral phenotype and neuronal calcium signaling

“…Levels of anti-dsDNA autoantibodies in serum and CSF were quantified using a fully-automated ELISA analyzer (EUROIMMUN Analyzer I) as previously described [ 59 ]. Briefly, 100 μl of each sample (1:50 dilution in PBS buffer) was transferred into a microtiter plate well containing antigen substrate of dsDNA complexed with nucleosomes (Anti-dsDNA-NcX ELISA, EUROIMMUN).…”

“…A Rotarod (ENV-575 M, Med Associates Inc.) was used to probe balance, muscle strength and acquisition of sensorimotor coordination, as described previously [ 59 , 76 ]. The Rotarod accelerated from 4 to 40 RPM over 5 min and the latency and speed at fall were recorded automatically.…”